826 results on '"Agaimy A."'
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2. Primäre Speicheldrüsentumoren aus Sicht der Pathologie
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Abbas Agaimy
- Subjects
Otorhinolaryngology - Published
- 2023
3. Role of Surgical Pathologist for the Detection of Immuno-oncologic Predictive Factors in Non-small Cell Lung Cancers
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Sambit K. Mohanty, Sourav K. Mishra, Mahul B. Amin, Abbas Agaimy, and Florian Fuchs
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Anatomy ,Pathology and Forensic Medicine - Published
- 2023
4. KRAS codon 12 mutations characterize a subset of de novo proliferating 'metaplastic' Warthin tumors
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Abbas Agaimy, Konstantinos Mantsopoulos, Heinrich Iro, and Robert Stoehr
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Cell Biology ,General Medicine ,Molecular Biology ,Pathology and Forensic Medicine - Abstract
Warthin tumor (WT; synonym: cystadenolymphoma) represents one of the most frequent salivary gland tumors with a frequency equaling or even outnumbering that of pleomorphic adenomas in some series. Histologically, the tumor displays tall columnar oncocytic cells, arranged into two cell-thick layers lining variably cystic glands within an organoid lymphoid stroma. Tumors with exuberant squamous metaplasia in response to FNA-induced or other types of tissue injury/infarction have been referred to as “metaplastic WTs.” However, the same terminology was used for tumors with variable mucinous cell and solid or stratified epidermoid proliferations (occasionally mimicking mucoepidermoid carcinoma), although the “metaplasia concept” has never been proven for the latter. We herein investigated 22 WTs showing prominent mucoepidermoid-like or solid oncocytoma-like proliferations without prior FNA or histological evidence of infarction/ trauma using the TruSight Tumor 15 gene panel and KRAS pyrosequencing. As a control, we tested 11 conventional WTs. No statistically significant differences were observed between the two subcohorts regarding patient’s age and tumor size. Six of 22 (27%) proliferating/ metaplastic WTs revealed oncogenic KRAS mutations clustering at codon 12 (exon 2), while all conventional tumors lacked these mutations. Our findings are in line with a neoplastic nature of the epidermoid/ mucoepidermoid proliferations in non-injured “metaplastic” Warthin tumors. We propose the descriptive term “de novo proliferating Warthin tumor” for this variant to distinguish it from infarcted/inflamed genuine metaplastic Warthin tumor.
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- 2023
5. Datasets for reporting of soft‐tissue sarcoma: recommendations from the International Collaboration on Cancer Reporting ( <scp>ICCR</scp> )
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Angelo Paolo Dei Tos, Fleur Webster, Abbas Agaimy, Judith Bovée, Brendan Dickson, Leona Doyle, Sarah Dry, Alessandro Gronchi, Meera Hameed, Chris Hemmings, Bernadette Liegl‐Atzwanger, Khin Thway, Andrew J Wagner, Jian Wang, Akihiko Yoshida, and Christopher Fletcher
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Histology ,General Medicine ,Pathology and Forensic Medicine - Published
- 2023
6. Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma
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Abbas Agaimy, Blaise A. Clarke, David L. Kolin, Cheng-Han Lee, Jen-Chieh Lee, W. Glenn McCluggage, Patrik Pöschke, Robert Stoehr, David Swanson, Gulisa Turashvili, Matthias W. Beckmann, Arndt Hartmann, Cristina R. Antonescu, and Brendan C. Dickson
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Adult ,Aged, 80 and over ,Leiomyoma ,Sarcoma, Endometrial Stromal ,Nuclear Proteins ,Soft Tissue Neoplasms ,Middle Aged ,Pathology and Forensic Medicine ,Endometrial Neoplasms ,Endometrial Stromal Tumors ,Uterine Neoplasms ,Biomarkers, Tumor ,Humans ,Surgery ,Female ,Neprilysin ,Anatomy ,Aged ,Histone Acetyltransferases - Abstract
With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.
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- 2023
7. <scp> TFG::MET </scp> ‐rearranged soft tissue tumor: A rare infantile neoplasm with a distinct low‐grade triphasic morphology
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Michael Michal, Nasir Ud Din, Marián Švajdler, Natálie Klubíčková, Nikola Ptáková, Veronika Hájková, Michal Michal, and Abbas Agaimy
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Cancer Research ,Genetics - Abstract
This article presents 2 cases of TFG::MET-rearranged mesenchymal tumor, an extremely rare molecular subset among an emerging group of mesenchymal neoplasms with kinase gene (NTRK, BRAF, RET and others) alterations. Both tumors were congenital, occurred in female patients and presented as huge masses on the trunk and thigh, measuring 18 and 20 cm in the largest dimension. Both cases showed identical areas with a distinctive triphasic morphology resembling fibrous hamartoma of infancy (FHI), consisting of haphazardly arranged ovoid to spindled cells traversed by variably cellular and hyalinized fascicles admixed with (most likely non-neoplastic) adipose tissue. In other areas, a high-grade infantile fibrosarcoma/malignant peripheral nerve sheath tumor-like (IFS/MPNST-like) morphology was present in both cases. While the first case co-expressed CD34 and S100 protein, the other case did not. When combined with the three previously reported MET-rearranged cases (of which two harbored TFG::MET fusion), 3/5 and 3/4 of MET-rearranged and TFG::MET fusion-associated tumors, respectively exhibited similar triphasic FHI-like low-grade morphology. This points towards the existence of a relatively distinct morphological subset among kinase-fusion-associated tumors which seems to be strongly associated with MET fusions. It seems some of these low-grade cases may transform into a high-grade variant with IFS/MPNST-like morphology as has been observed in other tumors with kinase gene fusions. While most cases seem to follow an indolent clinical course, the recognition of these tumors is clinically relevant as MET tyrosine kinase inhibitors might represent an effective treatment option for clinically aggressive or unresectable cases.
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- 2022
8. Expanding the molecular spectrum of gene fusions in endometrial stromal sarcoma: Novel subunits of the chromatin remodeling complexes <scp>PRC2</scp> and <scp>NuA4</scp> / <scp>TIP60</scp> as alternative fusion partners
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Josephine K. Dermawan, Nooshin Dashti, Sarah Chiang, Gulisa Turashvili, Brendan C. Dickson, Lora H. Ellenson, Martina Kirchner, Albrecht Stenzinger, Gunhild Mechtersheimer, Abbas Agaimy, and Cristina R. Antonescu
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Cancer Research ,Genetics - Published
- 2022
9. Panelsequenzierung in der Kopf-Hals-Onkologie am Beispiel von sinunasalen und Speicheldrüsenmalignomen
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Abbas Agaimy and Sarina K. Müller
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- 2022
10. Alterations in key signaling pathways in sinonasal tract melanoma. A molecular genetics and immunohistochemical study of 90 cases and comprehensive review of the literature
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Małgorzata Chłopek, Jerzy Lasota, Lester D.R. Thompson, Magdalena Szczepaniak, Alina Kuźniacka, Kinga Hińcza, Kamila Kubicka, Maciej Kaczorowski, Michael Newford, Yalan Liu, Abbas Agaimy, Wojciech Biernat, Monika Durzyńska, Ireneusz Dziuba, Arndt Hartmann, Shingo Inaguma, Ewa Iżycka-Świeszewska, Hiroyuki Kato, Janusz Kopczyński, Michal Michal, Michael Michal, Rafał Pęksa, Monika Prochorec-Sobieszek, Anna Starzyńska, Satoru Takahashi, Bartosz Wasąg, Artur Kowalik, and Markku Miettinen
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Male ,Proto-Oncogene Proteins B-raf ,Class I Phosphatidylinositol 3-Kinases ,TOR Serine-Threonine Kinases ,DNA Mutational Analysis ,Pathology and Forensic Medicine ,Mutation ,Paranasal Sinuses ,Humans ,RNA ,Female ,Melanoma ,Molecular Biology ,In Situ Hybridization, Fluorescence ,Paranasal Sinus Neoplasms ,Aged ,Signal Transduction - Abstract
Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.
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- 2022
11. Extrarenal renal cell carcinoma arising in the kidney proximity but without an identifiable renal primary – an intriguing dilemma: report of three cases and review of the literature
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Mehdi Mansoor, Morgan Young‐Speirs, Bing Ren, Geoffrey Gotto, Larissa Merten, Summit Sawhney, Farshid Siadat, Andres M Acosta, Abbas Agaimy, and Kiril Trpkov
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Male ,Histology ,Humans ,Female ,Lymph Nodes ,General Medicine ,Kidney ,Carcinoma, Renal Cell ,Kidney Neoplasms ,Pathology and Forensic Medicine - Abstract
To raise awareness of the existence of extrarenal renal cell carcinoma (RCC).We report three patients with extrarenal RCC found in the renal proximity, but unattached to the kidney. None had a history of RCC or an identifiable primary renal neoplasm at the time of the diagnosis and on follow-up. The patients included two males and one female aged 57, 77, and 63 years, respectively. One carcinoma was found in the perirenal tissue adjacent to the adrenal, one involved the adrenal gland, and one was a retroperitoneal mass found within the lymph nodes. Two extrarenal RCCs represented clear-cell RCCs and one was an unclassifiable RCC. No patient had evidence of metastases at presentation and disease progression during the follow-up. This report adds to the literature on this unusual clinical scenario and further supports the concept of extrarenal RCC, which is not a well-recognized clinical phenomenon. We also reviewed other similar reports documenting the absence of identifiable renal primaries in the setting of either disseminated metastatic disease or isolated distant metastases of presumed renal origin. Similarly, some carcinomas of apparent renal derivation have been also identified during a work-up of metastatic carcinomas of unknown primary.There should be an awareness of this unusual and intriguing clinical scenario that currently lacks a definitive explanation and standardized therapy strategies. Establishing a correct diagnosis may allow treatment with specific targeted therapies in selected clinical cases.
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- 2022
12. TIMP3::ALK fusions characterize a distinctive myxoid fibroblastic tumor of the vocal cords: a report of 7 cases
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Natálie Klubíčková, Michael Michal, Abbas Agaimy, Nina Zidar, Michal Pavlovský, Kenji Yorita, Petr Grossmann, Veronika Hájková, Nikola Ptáková, Petr Šteiner, and Michal Michal
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Male ,Tissue Inhibitor of Metalloproteinase-3 ,Receptor Protein-Tyrosine Kinases ,Vocal Cords ,Cell Biology ,General Medicine ,Middle Aged ,Immunohistochemistry ,Pathology and Forensic Medicine ,Biomarkers, Tumor ,Humans ,Female ,Proteoglycans ,Gene Fusion ,Molecular Biology - Abstract
We report 7 cases of an indolent, variably myxoid tumor of the vocal cords, characterized by overt cellular atypia with large cells containing intranuclear and intracytoplasmic vacuoles, delicate curvilinear vessels, and sparse inflammatory infiltrate. Six patients were male, aged 15 to 65 years, and 1 patient was a 54-year-old female. All tumors were located in the superficial portion of the vocal cord. One patient suffered a recurrence that was completely resected; all patients with available follow-up data currently have no evidence of disease. The tumors contained alternating areas with myxoid stroma and more compacted regions with tumor cells organized in short fascicles, interwoven with delicate curvilinear vasculature. Overt cellular atypia with large cells containing intranuclear and intracytoplasmic vacuoles or resembling ganglion cells was present in all cases but mitoses and necrosis were absent. ALK immunostaining was positive in all cases, while most tumors were negative for smooth muscle actin. Targeted RNA-sequencing revealed an identical TIMP3::ALK fusion with exon 1 of TIMP3 gene being fused with exon 12 of ALK gene in all analyzable cases. For various reasons discussed, it remains unclear whether this tumor represents a mere subtype of IMT or a separate entity. Nevertheless, it is a morphologically distinct and diagnostically challenging lesion that needs to be recognized by surgical pathologists in order to prevent overdiagnosis in this clinically very delicate area.
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- 2022
13. Recurrent VGLL3 fusions define a distinctive subset of spindle cell rhabdomyosarcoma with an indolent clinical course and striking predilection for the head and neck
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Abbas Agaimy, Josephine K. Dermawan, Iona Leong, Robert Stoehr, David Swanson, Ilan Weinreb, Lingxin Zhang, Cristina R. Antonescu, and Brendan C. Dickson
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Adult ,Male ,Cancer Research ,Soft Tissue Neoplasms ,Middle Aged ,Actins ,Desmin ,DNA-Binding Proteins ,Rhabdomyosarcoma ,Biomarkers, Tumor ,Genetics ,Humans ,Female ,Myogenin ,Aged ,Transcription Factors - Abstract
The mammalian Vestigial-like (VGLL) transcriptional cofactor family of proteins VGLL1-4 has recently emerged as an important player in the tumorigenesis of diverse neoplasms. The role of VGLL3 in soft tissue tumors is exemplified by its amplification in myxoinflammatory fibroblastic sarcoma and its rearrangement (fused to CHD7, CHD9, or MAMLD1) in hybrid schwannoma-perineurioma. This study characterizes a distinctive low-grade myogenic neoplasm with a striking predilection for the head and neck, characterized by VGLL3 fusions. The study includes five males and one female patient, aged 30-71 years (median, 56). Three tumors originated in the tongue, with one case each in the nasopharynx, oral cavity, and oropharynx. The VGLL3 fusion partners included TCF12 (n = 3), EP300 (n = 2), and PPARGC1A (n = 1). The tumor size range was 0.8-1.6 cm (all, but one, was1 cm). Histologically, all tumors displayed bland spindle to ovoid cells arranged into vague fascicular and diffuse patterns. Mitotic activity ranged from 1 to 7 per 10 HPFs. Five tumors were muscle-centered and infiltrative, and one was centered beneath nasopharyngeal mucosa. Immunohistochemistry revealed consistent expression of desmin (diffuse in four and patchy in two cases) associated with patchy smooth muscle actin expression (4/6), and focal reactivity for myogenin (5/6) and myoD1 (1/3). All patients were managed surgically; one patient each received adjuvant radio- or chemotherapy. Three patients with follow-up were without disease at 8, 19, and 60 months and one was alive with unknown disease status at 24 months. All VGLL3 fusions were in-frame and involved exon 2, fused with either TCF12 exon 16, EP300 exon 31, or PPARGC1A exon 5, respectively. This series characterizes a distinctive subset of spindle cell rhabdomyosarcoma (RMS) with a predilection for the head and neck in adults, defined by VGLL3 fusions, likely indolent behavior and limited rhabdomyoblastic differentiation. Further delineation of this entity and differentiation from more aggressive molecular subtypes of spindle cell RMS is mandatory to define the most appropriate therapeutic strategy and avoid overtreatment.
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- 2022
14. IgG4-related pseudotumours: a series of 12 cases and a review of the literature
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Maccagno, Andrea, Grosser, Bianca, Füzesi, László, Konukiewitz, Björn, Vlasenko, Dmytro, Weckermann, Dorothea, Raab, Stephan, Zenk, Johannes, Agaimy, Abbas, and Märkl, Bruno
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Male ,Immunoglobulin G ,Plasma Cells ,Submandibular Gland ,Humans ,Female ,Immunoglobulin G4-Related Disease ,Middle Aged ,Fibrosis ,Aged ,Autoimmune Diseases ,Pathology and Forensic Medicine - Abstract
IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ.
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- 2022
15. IgG4-related sclerosing thyroiditis (Riedel-Struma): a review of clinicopathological features and management
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Agata Czarnywojtek, Krzysztof Pietrończyk, Lester D. R. Thompson, Asterios Triantafyllou, Ewa Florek, Nadia Sawicka-Gutaj, Marek Ruchała, Maria Teresa Płazinska, Iain J. Nixon, Ashok R. Shaha, Mark Zafereo, Gregory William Randolph, Peter Angelos, Abir Al Ghuzlan, Abbas Agaimy, and Alfio Ferlito
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Cell Biology ,General Medicine ,Molecular Biology ,Pathology and Forensic Medicine - Abstract
We present a thorough review of the literature on Riedel thyroiditis (RT) with emphasis on aetiology, diagnosis and management, using the PubMed, Sinomed, and China National Knowledge Infrastructure databases. Although the exact aetiology of RT remains obscure, the histopathological features are consistent with a localized form of IgG4-related systemic disease (IgG4-RSD). Nevertheless, IgG4-RSD as a systemic fibroinflammatory disorder per se rarely affects the thyroid in the context of multiorgan manifestations. The initial diagnosis of RT is based on clinical history and imaging, but confirmation by histopathological examination is mandatory. In contrast to the historical surgical approach, glucocorticosteroid therapy is currently considered first line therapy, in line with the RT currently being viewed as a manifestation of, or analogous to, IgG4-RSD. For disease relapse, immunomodulatory agents (azathioprine, methotrexate, rituximab) can be used.
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- 2023
16. CREB fusion–associated epithelioid mesenchymal neoplasms of the female adnexa: three cases documenting a novel location of an emerging entity and further highlighting an ambiguous misleading immunophenotype
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Alexis Trecourt, Nicolas Macagno, Carine Ngo, Charles-André Philip, Jonathan Lopez, Joana Ferreira, Catarina Alves-Vale, Isabelle Ray-Coquard, Catherine Genestie, Abbas Agaimy, and Mojgan Devouassoux-Shisheboran
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Cell Biology ,General Medicine ,Molecular Biology ,Pathology and Forensic Medicine - Abstract
EWSR1/FUS-CREB-rearranged mesenchymal neoplasms are an emerging heterogeneous group of soft tissue tumors that encompasses low-grade lesions (angiomatoid fibrous histiocytoma/AFH) and a group of predominantly intra-abdominal aggressive sarcomas with epithelioid morphology and frequent keratin expression. Both entities occasionally harbor EWSR1::ATF1 fusions as alternate to the more frequent EWSR1/FUS::CREB1/CREM fusions. Although EWSR1/FUS-CREB-rearranged epithelioid malignant neoplasms have been described in diverse intra-abdominal sites, none involved the female adnexa. Herein, we describe three cases involving uterine adnexa in young females (41, 39, and 42-year-old); two associated with constitutional inflammatory symptoms. The tumors presented as a serosal surface mass of the ovary without parenchymal involvement (Case 1), as circumscribed nodule within ovarian parenchyma (Case 2), and as a periadnexal mass extending into the lateral uterine wall with lymph node metastasis (Case 3). They were composed of sheets and nests of large epithelioid cells with numerous stromal lymphocytes and plasma cells. The neoplastic cells expressed desmin and EMA, and variably WT1. One tumor expressed in addition AE1/AE3, MUC4, synaptophysin, chromogranin, and ALK. None expressed sex cord-associated markers. RNA sequencing identified EWSR1::ATF1 fusions in two cases and an EWSR1::CREM fusion in one. Exome-based RNA capture sequencing and clustering methods showed high transcriptomic proximity of tumor 1 with soft tissue AFH. This novel subset of female adnexal neoplasms should be included in the differential diagnosis of any epithelioid neoplasm involving female adnexa. Their aberrant immunophenotype can be misleading, underlining a wide spectrum of differential diagnosis.
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- 2023
17. PIK3CA mutation testing as a valuable molecular surrogate for lipomatosis of the median nerve: clinicopathological and molecular analysis of six cases
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Justus Osterloh, Abbas Agaimy, Frederick Fried, Robert Stoehr, Rolf Janka, Andreas Arkudas, and Raymund E. Horch
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Cell Biology ,General Medicine ,Molecular Biology ,Pathology and Forensic Medicine - Abstract
Lipomatosis of peripheral nerves (LPN, also known as fibrolipomatous or lipofibromatous hamartoma of peripheral nerves) is a very rare, benign, intraneural, tumorous lesion that predominantly involves the median nerve but may rarely affect any peripheral nerve. Recently, PIK3CA mutations have been reported in macrodactyly, a rare condition related to LPN, and in other localized lipomatous overgrowth syndromes. In this retrospective study, we report 6 cases of FPN involving the median nerve (4 of them identified among 570 patients with carpal tunnel syndrome who underwent surgical decompression at our center from 2012 to 2022 and two seen in consultation by one of the authors). All cases were diagnosed via biopsy or resection supplemented by MRI. Patients were 4 males and 2 females aged 23 to 60 years (mean 38 years). One patient with bilateral lesions had in addition extensive angiomatosis of the paravertebral region. Histological examination showed an abnormal amount of mature fatty tissue containing disordered fibrous bands, entrapping normal-looking nerve fibers with prominent perineurial and endoneurial fibrosis. Genetic analysis using snapshot assay constructed to detect hotspots mutations in PIK3CA revealed similar PIK3CA mutations (p.H1047R; c.3140A>G) in 5/6 cases (83.3%). Our study represents a further contribution to the literature on LPN and highlights the diagnostic value of PIK3CA mutation testing as surrogate tool in equivocal cases and in those lesions without associated macrodactyly, especially as the biopsy findings of this lesion are essentially nonspecific.
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- 2023
18. Clinicopathological, immunohistochemical, molecular-genetic and risk profiles of gastrointestinal stromal tumors in a cohort of Sudanese patients
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Nazik Elmalaika Husain, Ihsan Mohamed Osman, Ahmed Khalid, Ali Abdel Satir, Robert Stoehr, and Abbas Agaimy
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Gastrointestinal stromal tumour ,GIST ,risk stratification ,malignant behaviour ,risk assessment ,tumour rupture ,metastasis ,Imatinib ,genotyping ,KIT ,DOG1 ,General Medicine - Abstract
Background: Determining the risk of malignant behaviour and mutational status of gastrointestinal stromal tumours (GISTs) guide the management decision and allow optimal individualized patient treatment. Objectives: To determine clinicopathological, immunohistochemical (IHC), risk and KIT mutational findings of GISTs in Sudanese patients. Methods: Histological slides were reviewed, IHC for DOG-1 and CD117 performed and hotspot KIT mutations examined. The risk group was assigned using combined risk criteria. Results: 21 of the 36 patients (58.3%) were males (mean age, 54.83 ±12.57; range, 26-71). Abdominal pain and mass were the most frequent symptoms. Mean tumor size (±SD) was 11.6(±5.82) cm. Either CD117, DOG1 or both were positive in all cases. Using risk criteria, 33.3% (n=12) were clinically malignant at presentation, 13.9% (n=5) high risk, 16.7% (n=6) intermediate, 27.8% (n=10) low risk and 2.8% (n=1) very low risk. Sixteen of 23 (70%) tested cases had KIT (14 exon 11 and two exon 9) mutations. Six tumors were wild type. Exon 11 deletions (p.I563-L576 del and p.V559-N566delinsD) significantly correlate withdisease recurrence (p-value: 0.028). Conclusions: Sudanese patients with GIST tend to present late. Nearly half of them correspond to the malignant/high-risk category. The frequency of KIT mutations (79.31%) is in line with the literature. Keywords: Gastrointestinal stromal tumour; GIST; risk stratification; malignant behaviour; risk assessment; tumour rupture; metastasis; Imatinib; genotyping; KIT; DOG1.
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- 2023
19. The Challenge of 'Monomorphic' Mucoepidermoid Carcinoma—Report of a Rare Case with Pure Spindle-Clear Cell Morphology
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Xinyi Qu, Edwin Jun Chen Chew, Sathiyamoorthy Selvarajan, Bingcheng Wu, Abbas Agaimy, and Fredrik Petersson
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Oncology ,Otorhinolaryngology ,Pathology and Forensic Medicine - Published
- 2023
20. DNA methylation-based classification of sinonasal tumors
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Philipp Jurmeister, Stefanie Glöß, Renée Roller, Maximilian Leitheiser, Simone Schmid, Liliana H. Mochmann, Emma Payá Capilla, Rebecca Fritz, Carsten Dittmayer, Corinna Friedrich, Anne Thieme, Philipp Keyl, Armin Jarosch, Simon Schallenberg, Hendrik Bläker, Inga Hoffmann, Claudia Vollbrecht, Annika Lehmann, Michael Hummel, Daniel Heim, Mohamed Haji, Patrick Harter, Benjamin Englert, Stephan Frank, Jürgen Hench, Werner Paulus, Martin Hasselblatt, Wolfgang Hartmann, Hildegard Dohmen, Ursula Keber, Paul Jank, Carsten Denkert, Christine Stadelmann, Felix Bremmer, Annika Richter, Annika Wefers, Julika Ribbat-Idel, Sven Perner, Christian Idel, Lorenzo Chiariotti, Rosa Della Monica, Alfredo Marinelli, Ulrich Schüller, Michael Bockmayr, Jacklyn Liu, Valerie J. Lund, Martin Forster, Matt Lechner, Sara L. Lorenzo-Guerra, Mario Hermsen, Pascal D. Johann, Abbas Agaimy, Philipp Seegerer, Arend Koch, Frank Heppner, Stefan M. Pfister, David T. W. Jones, Martin Sill, Andreas von Deimling, Matija Snuderl, Klaus-Robert Müller, Erna Forgó, Brooke E. Howitt, Philipp Mertins, Frederick Klauschen, David Capper, Jurmeister, Philipp, Glöß, Stefanie, Roller, Renée, Leitheiser, Maximilian, Schmid, Simone, Mochmann, Liliana H, Payá Capilla, Emma, Fritz, Rebecca, Dittmayer, Carsten, Friedrich, Corinna, Thieme, Anne, Keyl, Philipp, Jarosch, Armin, Schallenberg, Simon, Bläker, Hendrik, Hoffmann, Inga, Vollbrecht, Claudia, Lehmann, Annika, Hummel, Michael, Heim, Daniel, Haji, Mohamed, Harter, Patrick, Englert, Benjamin, Frank, Stephan, Hench, Jürgen, Paulus, Werner, Hasselblatt, Martin, Hartmann, Wolfgang, Dohmen, Hildegard, Keber, Ursula, Jank, Paul, Denkert, Carsten, Stadelmann, Christine, Bremmer, Felix, Richter, Annika, Wefers, Annika, Ribbat-Idel, Julika, Perner, Sven, Idel, Christian, Chiariotti, Lorenzo, Della Monica, Rosa, Marinelli, Alfredo, Schüller, Ulrich, Bockmayr, Michael, Liu, Jacklyn, Lund, Valerie J, Forster, Martin, Lechner, Matt, Lorenzo-Guerra, Sara L, Hermsen, Mario, Johann, Pascal D, Agaimy, Abba, Seegerer, Philipp, Koch, Arend, Heppner, Frank, Pfister, Stefan M, Jones, David T W, Sill, Martin, von Deimling, Andrea, Snuderl, Matija, Müller, Klaus-Robert, Forgó, Erna, Howitt, Brooke E, Mertins, Philipp, Klauschen, Frederick, and Capper, David
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Proteomics ,Multidisciplinary ,Carcinoma ,DNA Helicases ,Reproducibility of Results ,Nuclear Proteins ,General Physics and Astronomy ,General Chemistry ,DNA Methylation ,General Biochemistry, Genetics and Molecular Biology ,Humans ,ddc:610 ,Technology Platforms ,Transcription Factors - Abstract
The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs.
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- 2022
21. Sinonasal mixed transitional epithelial-seromucinous papillary glandular neoplasms with BRAF p.V600E mutations — sinonasal analogues to the sialadenoma papilliferum family tumors
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Simmi Patel, Carl H. Snyderman, Sarina K. Müller, Abbas Agaimy, and Raja R. Seethala
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Cell Biology ,General Medicine ,Molecular Biology ,Pathology and Forensic Medicine - Published
- 2022
22. Supplementary Table S2 from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
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Sequences of primers and probes used for quantification of genomic fusion sequences
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- 2023
23. Supplementary Table S1 from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
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Sequences of primers used in nested multiplex PCR assays
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- 2023
24. Data from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Wolfgang Hartmann, Tobias Bäuerle, Abbas Agaimy, Eleni M. Tomazou, Peter Peneder, Adrian M Stütz, Christian Schmidkonz, Jakob Zierk, Andreas Ranft, Johanna Eiblwieser, and Manuela Krumbholz
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Purpose:We evaluated the predictive and prognostic value of circulating tumor DNA (ctDNA) in patients with Ewing sarcoma (EWS) treated in the EWING2008 trial.Experimental Design:Plasma samples from 102 patients with EWS enrolled in the EWING2008 trial were obtained before and during induction chemotherapy. Genomic EWSR1 fusion sequence spanning primers and probes were used for highly specific and sensitive quantification of the levels of ctDNA by digital droplet PCR. ctDNA levels were correlated to established clinical risk factors and outcome parameters.Results:Pretreatment ctDNA copy numbers were correlated with event-free and overall survival. The reduction in ctDNA levels below the detection limit was observed in most cases after only two blocks of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) induction chemotherapy. The persistence of ctDNA after two VIDE blocks was a strong predictor of poor outcomes. ctDNA levels correlated well with most established clinical risk factors; an inverse correlation was found only for the histologic response to induction therapy. ctDNA levels did not provide simple representations of tumor volume, but integrated information from various tumor characteristics represented an independent EWS tumor marker with predictive and prognostic value.Conclusions:ctDNA copy number in the plasma of patients with EWS is a quantifiable parameter for early risk stratification and can be used as a dynamic noninvasive biomarker for early prediction of treatment response and outcome of patients.
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- 2023
25. Figure S2 from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Wolfgang Hartmann, Tobias Bäuerle, Abbas Agaimy, Eleni M. Tomazou, Peter Peneder, Adrian M Stütz, Christian Schmidkonz, Jakob Zierk, Andreas Ranft, Johanna Eiblwieser, and Manuela Krumbholz
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Event-free survival (EFS) and overall survival (OS) by sex, age at diagnosis, pelvis localization, tumor volume, presence of metastases, and histological response in patients with EWS.
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- 2023
26. Data from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
- Abstract
Purpose: The application of the tumor-specific genomic fusion sequence as noninvasive biomarker for therapy monitoring in Ewing sarcoma (EwS) has been evaluated.Experimental Design: EwS xenograft mouse models were used to explore detectability in small plasma volumes and correlation of genomic EWSR1-FLI1 copy numbers with tumor burden. Furthermore, 234 blood samples from 20 EwS patients were analyzed before and during multimodal treatment. EWSR1 fusion sequence levels in patients' plasma were quantified using droplet digital PCR and compared with tumor volumes calculated from MRI or CT imaging studies.Results: Kinetics of EWSR1 fusion sequence copy numbers in the plasma are correlated with changes of the tumor volume in patients with localized and metastatic disease. The majority of patients showed a fast reduction of cell-free tumor DNA (ctDNA) during initial chemotherapy. Recurrence of increasing ctDNA levels signalized relapse development.Conclusions: Genomic fusion sequences represent promising noninvasive biomarkers for improved therapy monitoring in EwS. Until now, response assessment is largely based on MRI and CT imaging, implying restrictions on closely repeated performance and limitations on the differentiation between vital tumor and reactive stromal tissue. Particularly in patients with prognostic unfavorable disseminated disease, ctDNA is a valuable addition for the assessment of therapy response. Clin Cancer Res; 22(17); 4356–65. ©2016 AACR.
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- 2023
27. Figure S4 from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Wolfgang Hartmann, Tobias Bäuerle, Abbas Agaimy, Eleni M. Tomazou, Peter Peneder, Adrian M Stütz, Christian Schmidkonz, Jakob Zierk, Andreas Ranft, Johanna Eiblwieser, and Manuela Krumbholz
- Abstract
Quantified mean ctDNA levels (fusion gene/ALB copies) before (VIDE1A) and after (VIDE1E) the first chemotherapy block separated according to different clinical risk criteria. The upper graphs show results for localized disease, the lower graphs show results for metastatic disease.
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- 2023
28. Figure S3 from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Wolfgang Hartmann, Tobias Bäuerle, Abbas Agaimy, Eleni M. Tomazou, Peter Peneder, Adrian M Stütz, Christian Schmidkonz, Jakob Zierk, Andreas Ranft, Johanna Eiblwieser, and Manuela Krumbholz
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Event-free survival (EFS) and overall survival (OS) by quantified pretreatment ctDNA levels for patients with localized or metastatic disease.
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- 2023
29. Supplementary Figure S1 from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
- Abstract
Tumor engraftment in NMRI nu/nu and NSG mice after s.c. (A) and i.v. (B) injection of EWSR1-FLI1 positive cell lines EwS type 1 (A673 and TC-71) or type 2 (VH-64 and RD-ES). (C) Localization of metastases after i.v. injection of EwS cells in NMRI nu/nu and NSG mice. T2-weighted images from ultra high field MRI show the presence of organ metastases in NSG mice ex vivo (Lu, Lung; H, Heart; B, Bone; M, Muscle; Li, Liver; K, Kidney; O, Ovary; *, Tumor). H&E stain and CD99+ immunostaining show tumor infiltration with high proliferation rate (60%).
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- 2023
30. Supplementary Figure S2 from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
- Abstract
Individual genomic EWSR1-FLI1 or EWSR1-ERG fusion sequences. Repeat regions are highlighted in gray.
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- 2023
31. Supplementary Figure S3 from Genomic EWSR1 Fusion Sequence as Highly Sensitive and Dynamic Plasma Tumor Marker in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Heribert Juergens, Wolfgang Hartmann, Eva Wardelmann, Joerg Juengert, Benjamin Frey, Abbas Agaimy, Torsten Fritscher, Clarissa Gillmann, Tobias Bäuerle, Benedikt Steif, Julia Hellberg, and Manuela Krumbholz
- Abstract
ctDNA levels calculated by normalization of the EWSR1-FLI1 signal to the signal of the single copy gene albumin compared to normalization with the plasma volume used for DNA extraction. Plasma sample quality was monitored by reference gene (albumin) per volume.
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- 2023
32. Figure S1 from Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma
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Markus Metzler, Uta Dirksen, Wolfgang Hartmann, Tobias Bäuerle, Abbas Agaimy, Eleni M. Tomazou, Peter Peneder, Adrian M Stütz, Christian Schmidkonz, Jakob Zierk, Andreas Ranft, Johanna Eiblwieser, and Manuela Krumbholz
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Composition of the study groups with a good histological response and poor histological response with regard to tumor volume, presence of metastases, and osseous localization.
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- 2023
33. Effect of postoperative systemic prednisolone on short-term and long-term outcomes in chronic rhinosinusitis with nasal polyps: A multi-centered randomized clinical trial
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Mueller, Sarina K., Wendler, Olaf, Mayr, Susanne, Traxdorf, Maximilian, Hosemann, Werner, Olze, Heidi, Steinhart, Helmut, Wiegand, Susanne, Teymoortash, Afshin, Kuehnel, Thomas, Hackenberg, Stephan, Hummel, Thomas, Ambrosch, Petra, Fazel, Azita, Schick, Bernhard, Baenkler, Hanns-Wolf, Koch, Michael, Buerner, Harald, Mantsopoulos, Konstantinos, Grundtner, Philipp, Nocera, Angela, Agaimy, Abbas, Bleier, Benjamin, and Iro, Heinrich
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Immunology ,Immunology and Allergy ,ddc:610 - Abstract
IntroductionThe objective of this study was to determine whether postoperative additive systemic steroid administration in chronic rhinosinusitis with nasal polyps (CRSwNP) impacted selected endoscopic, subjective and objective outcome measures.MethodsThis was a prospective, randomized, double-blind, placebo-controlled, noninferiority multicenter trial of n=106 patients with CRSwNP. All patients underwent primary functional endoscopic sinus surgery (FESS) followed by topical nasal steroids. Patients were randomized to a systemic steroid or placebo for 1 month. Patients were followed up for 2 years over 9 time points. The primary outcome measures were the differences between groups with respect to the nasal polyp score (NPS) and sinonasal quality of life (SNQoL). Secondary outcome measures included interactions with respect to the Lund-Kennedy score (LKS), sinonasal symptoms, general quality of life (GQoL), 16-item odor identification test scores, recurrence rates, need for revision surgery and mucus biomarker levels.Results106 patients were randomized to either the placebo or the systemic steroid group (n=53 per group). Postoperative systemic steroids were not superior to placebo with respect to all primary (p= 0.077) and secondary outcome measures (p>0.05 for all). Reported adverse events were similar between the two groups.ConclusionIn conclusion, the addition of postoperative systemic steroids after primary FESS did not confer a benefit over topical steroid nasal spray alone with respect to NPS, SNQOL, LKS, GQOL, sinonasal symptoms, smell scores, recurrence rates, the need for revision surgery or biomarkers over a short-term follow-up of up to 9 months and a long-term follow-up of up to 24 months in CRSwNP patients. Functional endoscopic surgery did, however, show a strong effect on all outcome measures, which remained relatively stable up to the endpoint at 2 years.
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- 2023
34. GAB1::ABL1 fusions define a distinctive soft tissue neoplasm, with variable perineurial differentiation, and a predilection for children and young adults
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Abbas Agaimy, Raul Perret, Elizabeth G. Demicco, John Gross, Yajuan J. Liu, Rihab Azmani, Carsten Engelmann, Christoph Schubart, Joosep Seppet, Robert Stoehr, François Le Loarer, and Brendan C. Dickson
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Cancer Research ,Genetics - Published
- 2023
35. HCCs lacking arterial phase hyperenhancement (APHE) on contrast-enhanced ultrasound (CEUS) – a diagnostic challenge. Findings from the prospective multicenter DEGUM CEUS HCC trial
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Deike Strobel, Abbas Agaimy, Daniel Jesper, Sebastian Zundler, and Barbara Schellhaas
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Radiology, Nuclear Medicine and imaging - Abstract
Objectives Hepatocellular carcinoma (HCC) upon contrast-enhanced ultrasound (CEUS) typically shows arterial phase hyperenhancement (APHE), followed by late (> 60 seconds) and mild contrast washout (WO). Although APHE is considered as the hallmark of HCC, it can be absent in some HCCs. Thus, we explored which sonomorphological and histopathological features of HCC are associated with a lack of APHE upon CEUS. Methods Focal liver lesions in high-risk patients for HCC were assessed with CEUS following a standardized protocol in a prospective multi-center real-life setting. CEUS patterns in HCC were assessed, and tumour and patient characteristics were compared for HCCs with and without APHE. Results 316 patients with HCC were recruited (cirrhosis, 76.9%). APHE occurred in 271/316 HCCs (85.8%). A lack of APHE was associated with portal vein thrombosis, tumour infiltration of the liver vessels (p Conclusion Correlation with histopathological findings support the fact that HCCs with a lack of APHE in CEUS are a heterogeneous group. The examiner has to be aware that particularly HCCs with portal vein thrombosis or macro-invasion of the liver vessels may lack APHE.
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- 2023
36. Colon Cancer Microbiome Landscaping: Differences in Right- and Left-Sided Colon Cancer and a Tumor Microbiome-Ileal Microbiome Association
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Barbara Kneis, Stefan Wirtz, Klaus Weber, Axel Denz, Matthias Gittler, Carol Geppert, Maximilian Brunner, Christian Krautz, Alexander Reinhard Siebenhüner, Robert Schierwagen, Olaf Tyc, Abbas Agaimy, Robert Grützmann, Jonel Trebicka, Stephan Kersting, and Melanie Langheinrich
- Subjects
Organic Chemistry ,microbiome ,left-sided colon cancer ,gut microbiome ,General Medicine ,Catalysis ,tumor microbiome ,Computer Science Applications ,Inorganic Chemistry ,colon cancer ,ddc:610 ,Physical and Theoretical Chemistry ,right-sided colon cancer ,Molecular Biology ,Spectroscopy - Abstract
In the current era of precision oncology, it is widely acknowledged that CRC is a heterogeneous disease entity. Tumor location (right- or left-sided colon cancer or rectal cancer) is a crucial factor in determining disease progression as well as prognosis and influences disease management. In the last decade, numerous works have reported that the microbiome is an important element of CRC carcinogenesis, progression and therapy response. Owing to the heterogeneous nature of microbiomes, the findings of these studies were inconsistent. The majority of the studies combined colon cancer (CC) and rectal cancer (RC) samples as CRC for analysis. Furthermore, the small intestine, as the major site for immune surveillance in the gut, is understudied compared to the colon. Thus, the CRC heterogeneity puzzle is far from being solved, and more research is necessary for prospective trials that separately investigate CC and RC. Our prospective study aimed to map the colon cancer landscape using 16S rRNA amplicon sequencing in biopsy samples from the terminal ileum, healthy colon tissue, healthy rectal tissue and tumor tissue as well as in preoperative and postoperative stool samples of 41 patients. While fecal samples provide a good approximation of the average gut microbiome composition, mucosal biopsies allow for detecting subtle variations in local microbial communities. In particular, the small bowel microbiome has remained poorly characterized, mainly because of sampling difficulties. Our analysis revealed the following: (i) right- and left-sided colon cancers harbor distinct and diverse microbiomes, (ii) the tumor microbiome leads to a more consistent cancer-defined microbiome between locations and reveals a tumor microbiome–ileal microbiome association, (iii) the stool only partly reflects the microbiome landscape in patients with CC, and (iv) mechanical bowel preparation and perioperative antibiotics together with surgery result in major changes in the stool microbiome, characterized by a significant increase in the abundance of potentially pathogenic bacteria, such as Enterococcus. Collectively, our results provide new and valuable insights into the complex microbiome landscape in patients with colon cancer.
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- 2023
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37. Clinical, histopathological and molecular features of dedifferentiated melanomas : An EORTC Melanoma Group Retrospective Analysis
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Hench, Juergen, Mihic-Probst, Daniela, Agaimy, Abbas, Frank, Stephan, Meyer, Peter, Hultschig, Claus, Simi, Sara, Alos, Lucia, Balamurugan, Thiagarajah, Blokx, Willeke, Bosisio, Francesca, Cappellesso, Rocco, Griewank, Klaus, Hadaschik, Eva, van Kempen, Léon, Kempf, Werner, Lentini, Maria, Mazzucchelli, Luca, Rinaldi, Gaetana, Rutkowski, Piotr, Schadendorf, Dirk, Schilling, Bastian, Szumera-Cieckiewicz, Anna, van den Oord, Joost, Mandalà, Mario, Massi, Daniela, and EORTC Melanoma Group
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Cancer Research ,Oncology ,Medizin ,Human medicine - Abstract
PURPOSE: Dedifferentiated melanoma (DedM) poses significant diagnostic challenges. We aimed to investigate the clinical, histopathological and molecular features of DedM. Methylation signature (MS) and copy number profiling (CNP) were carried out in a subgroup of cases.PATIENTS AND METHODS: A retrospective series of 78 DedM tissue samples from 61 patients retrieved from EORTC (European Organisation for Research and Treatment of Cancer) Melanoma Group centres were centrally reviewed. Clinical and histopathological features were retrieved. In a subgroup of patients, genotyping through Infinium Methylation microarray and CNP analysis was carried out.RESULTS: Most patients (60/61) had a metastatic DedM showing most frequently an unclassified pleomorphic, spindle cell, or small round cell morphology akin to undifferentiated soft tissue sarcoma, rarely associated with heterologous elements. Overall, among 20 successfully analysed tissue samples from 16 patients, we found retained melanoma-like MS in only 7 tissue samples while a non-melanoma-like MS was observed in 13 tissue samples. In two patients from whom multiple specimens were analysed, some of the samples had a preserved cutaneous melanoma MS while other specimens exhibited an epigenetic shift towards a mesenchymal/sarcoma-like profile, matching the histological features. In these two patients, CNP was largely identical across all analysed specimens, in line with their common clonal origin, despite significant modification of their epigenome.CONCLUSIONS: Our study further highlights that DedM represents a real diagnostic challenge. While MS and genomic CNP may help pathologists to diagnose DedM, we provide proof-of-concept that dedifferentiation in melanoma is frequently associated with epigenetic modifications.
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- 2023
38. Fusion‐positive skin/adnexal carcinomas
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Abbas Agaimy
- Subjects
Cancer Research ,Oncogene Proteins, Fusion ,Carcinoma ,Genetics ,Humans ,Nuclear Proteins ,Gene Fusion ,Immunohistochemistry ,Neoplasm Proteins ,Transcription Factors - Abstract
Gene fusions have been increasingly identified as central events driving oncogenesis in a variety of benign and malignant neoplasms of different histogenesis originating in diverse organs. While some fusion-driven neoplasms may occur at any body site, certain genotypes and their associated phenotypic entities cluster to specific body site/organ, albeit with variable frequencies among anatomic locations. In the last two decades, several skin adnexal entities driven by specific fusions have been described; some of them represent new entities (eg, secretory carcinoma harboring NTRK fusions), while others are old established entities with newly discovered underlying gene fusions (eg, poroid neoplasms harboring NUTM1, YAP1, and WWTR1 fusions). While limited availability of next generation sequencing tools in routine practice has largely limited and delayed discovery of fusions in old entities, the increasing availability of novel immunoantibodies as surrogates to recognize gene fusions (such as NUT and YAP1 immunohistochemistry) represents a relatively cheap, quick, and reliable routine tool for their proper recognition and appropriate classification. This review highlights the main, recently defined skin adnexal carcinomas carrying gene fusions.
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- 2022
39. Eosinophilic vacuolated tumor (EVT) of kidney demonstrates sporadic TSC/MTOR mutations: next-generation sequencing multi-institutional study of 19 cases
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Mihaela Farcaş, Zoran Gatalica, Kiril Trpkov, Jeffrey Swensen, Ming Zhou, Reza Alaghehbandan, Sean R. Williamson, Cristina Magi-Galluzzi, Anthony J. Gill, Maria Tretiakova, Jose I. Lopez, Delia Perez Montiel, Maris Sperga, Eva Comperat, Fadi Brimo, Asli Yilmaz, Farshid Siadat, Ankur Sangoi, Yuan Gao, Nikola Ptákova, Levente Kuthi, Kristyna Pivovarcikova, Joanna Rogala, Abbas Agaimy, Arndt Hartmann, Cristoph Fraune, Boris Rychly, Pavel Hurnik, Dušan Durcansky, Michael Bonert, Georgios Gakis, Michal Michal, Milan Hora, and Ondrej Hes
- Subjects
Adult ,Male ,Adolescent ,DNA Copy Number Variations ,TOR Serine-Threonine Kinases ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Kidney ,Carotenoids ,Kidney Neoplasms ,Pathology and Forensic Medicine ,Young Adult ,Mutation ,Biomarkers, Tumor ,Humans ,Female ,Neoplasm Recurrence, Local ,Vitamin A ,Carcinoma, Renal Cell ,Aged - Abstract
A distinct renal tumor has recently been described as "high-grade oncocytic renal tumor" and "sporadic renal cell carcinoma with eosinophilic and vacuolated cytoplasm". The Genitourinary Pathology Society (GUPS) consensus proposed a unifying name "eosinophilic vacuolated tumor" (EVT) for this emerging entity. In this multi-institutional study, we evaluated 19 EVTs, particularly their molecular features and mutation profile, using next-generation sequencing. All cases were sporadic and none of the patients had a tuberous sclerosis complex. There were 8 men and 11 women, with a mean age of 47 years (median 50; range 15-72 years). Average tumor size was 4.3 cm (median 3.8 cm; range 1.5-11.5 cm). All patients with available follow-up data (18/19) were alive and without evidence of disease recurrence or progression during the follow-up, ranging from 12 to 198 months (mean 56.3, median 41.5 months). The tumors were well circumscribed, but lacked a well-formed capsule, had nested to solid growth, focal tubular architecture, and showed ubiquitous, large intracytoplasmic vacuoles, round to oval nuclei, and prominent nucleoli. Immunohistochemically, cathepsin K, CD117, CD10, and antimitochondrial antigen were expressed in all cases. Other positive stains included: PAX8, AE1/AE3 and CK18. CK7 was typically restricted only to rare scattered cells. Vimentin, HMB45, melan-A, and TFE3 were negative in all cases. All tumors showed retained SDHB. All cases (19/19) showed non-overlapping mutations of the mTOR pathway genes: TSC1 (4), TSC2 (7), and MTOR (8); one case with MTOR mutation showed a coexistent RICTOR missense mutation. Low mutational rates were found in all samples (ranged from 0 to 6 mutations/Mbp). Microsatellite instability and copy number variations were not found in any of the 17 analyzable cases. EVT represents an emerging renal entity that shows a characteristic and readily identifiable morphology, consistent immunohistochemical profile, indolent behavior, and mutations in either TSC1, TSC2, or MTOR genes.
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- 2022
40. Expression of Prostate-specific Membrane Antigen (PSMA) in Papillary Renal Cell Carcinoma - Overview and Report on a Large Multicenter Cohort
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Stefanie Zschäbitz, Franziska Erlmeier, Christine Stöhr, Edwin Herrmann, Iris Polifka, Abbas Agaimy, Lutz Trojan, Philipp Ströbel, Frank Becker, Christian Wülfing, Peter Barth, Michael Stöckle, Michael Staehler, Christian Stief, Axel Haferkamp, Markus Hohenfellner, Stephan Macher-Göppinger, Bernd Wullich, Joachim Noldus, Walburgis Brenner, Frederik C. Roos, Bernhard Walter, Wolfgang Otto, Maximilian Burger, Andres Jan Schrader, Yvonne Mondorf, Arndt Hartmann, Philipp Ivanyi, and Sandra Steffens
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Oncology - Abstract
Prostate specific membrane antigen (PSMA) is an emerging diagnostic and therapeutic target in prostate cancer.
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- 2022
41. Dysphonia as a Presenting Symptom of a Giant Left Atrial Sarcoma Developing within Five Years
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Mohamed Elbayomi, Ehab Nooh, Michael Weyand, Abbas Agaimy, and Frank Harig
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ddc:610 - Abstract
An 83-year-old woman presented with a new onset of dyspnea and dysphonia. Physical examination revealed no abnormalities. Computerized tomography, bidimensional echocardiography, and cardiac magnetic resonance confirmed the presence of a cardiac mass in the left atrium. Surgical resection was uneventful and showed the origin of the mass in the ostium of the left inferior pulmonary vein. Histological evaluation revealed undifferentiated pleomorphic sarcoma with myxoid features. This case highlights the importance of considering cardiac neoplasms as a rare differential diagnosis, including rare and misleading clinical presentations.
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- 2022
42. Mesenchymale Tumoren und tumorartige Veränderungen des Gastrointestinaltraktes
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Abbas Agaimy
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Pathology and Forensic Medicine - Published
- 2021
43. Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments
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Arndt Hartmann, Ondrej Hes, Kiril Trpkov, and Abbas Agaimy
- Subjects
Pathology ,medicine.medical_specialty ,biology ,Carcinoma ,Vimentin ,medicine.disease ,Kidney Neoplasms ,Pathology and Forensic Medicine ,Surgical pathology ,Immunophenotyping ,Renal cell carcinoma ,Giant cell ,Biomarkers, Tumor ,medicine ,biology.protein ,Humans ,Immunohistochemistry ,Female ,SMARCB1 ,Carcinoma, Renal Cell - Abstract
Loss of the morphological and immunophenotypic characteristics of a neoplasm is a well-known phenomenon in surgical pathology and occurs across different tumor types in almost all organs. This process may be either partial, characterized by transition from well differentiated to undifferentiated tumor component (=dedifferentiated carcinomas) or complete (=undifferentiated carcinomas). Diagnosis of undifferentiated carcinoma is significantly influenced by the extent of sampling. Although the concept of undifferentiated and dedifferentiated carcinoma has been well established for other organs (e.g. endometrium), it still has not been fully defined for urological carcinomas. Accordingly, undifferentiated/ dedifferentiated genitourinary carcinomas are typically lumped into the spectrum of poorly differentiated, sarcomatoid, or unclassified (NOS) carcinomas. In the kidney, dedifferentiation occurs across all subtypes of renal cell carcinoma (RCC), but certain genetically defined RCC types (SDH-, FH- and PBRM1- deficient RCC) seem to have inherent tendency to dedifferentiate. Histologically, the undifferentiated component displays variable combination of four patterns: spindle cells, pleomorphic giant cells, rhabdoid cells, and undifferentiated monomorphic cells with/without prominent osteoclastic giant cells. Any of these may occasionally be associated with heterologous mesenchymal component/s. Their immunophenotype is often simple with expression of vimentin and variably pankeratin or EMA. Precise subtyping of undifferentiated (urothelial versus RCC and the exact underlying RCC subtype) is best done by thorough sampling supplemented as necessary by immunohistochemistry (e.g. FH, SDHB, ALK) and/ or molecular studies. This review discusses the morphological and molecular genetic spectrum and the recent develoments on the topic of dedifferentiated and undifferentiated genitourinary carcinomas.
- Published
- 2021
44. SMARCB1(INI1)-defizientes Nierenzellkarzinom: medullär und darüber hinaus
- Author
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Arndt Hartmann and Abbas Agaimy
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,business ,Pathology and Forensic Medicine - Abstract
In den letzten Jahrzehnten erlangte der Chromatin-remodulierende SWI/SNF-Komplex eine zentrale Rolle in der molekularen Pathogenese diverser Neoplasien. Die nosologische Klassifikation diverser Tumoren richtet sich zunehmend nach dem zugrunde liegenden SWI/SNF-Defekt. In der Niere gilt der Verlust von SMARCB1(INI1), einer der bedeutsamen SWI/SNF-Komponenten, als definierend fur das medullare Karzinom und den fruhkindlichen malignen Rhabdoidtumor. Die Diagnose beider sehr seltenen Entitaten basiert auf demografischen, klinisch-pathologischen und genetischen (SMARCB1-Inaktivierung) Charakteristika. Zudem gilt eine Sichelzellanamie als Voraussetzung fur die Diagnose eines medullaren Nierenkarzinoms. Neuere Erkenntnisse zeigen, dass eine SMARCB1-Inaktivierung auch sekundar in diversen sonstigen Tumorentitaten auftreten kann. SMARCB1-defiziente Nierentumoren lassen sich in 3 Hauptkategorien unterteilen: 1. primar (de novo) durch eine SMARCB1-Inaktivierung getriebene, histologisch und klinisch definierte spezifische Entitaten (das medullare Nierenkarzinom und der Rhabdoidtumor), 2. SMARCB1-defiziente Nierenzellkarzinom(NZK)-Varianten mit der Morphologie eines Sammelrohrkarzinoms (Ductus-Bellini-Karzinom) oder eines high-grade papillaren NZK (papillar Typ 2) bzw. einer vollig undifferenzierten (anaplastischen) Morphologie und 3. dedifferenzierte (biphasische) NZK mit einer variablen undifferenzierten SMARCB1-defizienten Komponente. Letztere Gruppe leitet sich meist aus einem klarzelligen, seltener aus einem papillaren oder einem chromophoben NZK ab. Im Folgenden werden die definierenden Aspekte SMARCB1-defizienter Nierentumore dargestellt und ihre aktuelle Klassifikation besprochen. Alle SMARCB1-defizienten Karzinome haben einen aggressiven klinischen Verlauf, sodass eine exakte Diagnose als Voraussetzung fur Studien mit Anwendung neuer Therapien wichtig ist.
- Published
- 2021
45. Recurrent EWSR1::COLCA2 Fusions Define a Novel Sarcoma With Spindle/Round Cell Morphology and Strong Predilection for the Sinonasal Tract
- Author
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Abbas Agaimy, Martina Baněčková, John De Almeida, Brendan C. Dickson, Arno Dimmler, Wolfgang Hartmann, Marick Laé, Jessica Pablik, Christoph Schubart, Alena Skálová, Robert Stoehr, Marcel Trautmann, Eva Wardelmann, Michel Wassef, and Ilan Weinreb
- Subjects
Surgery ,Anatomy ,Pathology and Forensic Medicine - Abstract
The last 2 decades have attended a dynamic evolution in the nosology of poorly differentiated sinonasal tract malignancies, with several new molecularly defined entities having been described in addition to delineation of the genetic driver/s of some established older entities. These discoveries, however, mostly concerned epithelial-derived neoplasms (carcinomas). Adamantinoma-like Ewing sarcoma and biphenotypic sinonasal sarcoma are the major representatives of the newly defined mesenchymal categories. The colorectal cancer associated 2 (COLCA2) has been discovered recently as a colorectal cancer risk gene locus, but fusions involving this gene have not been well characterized. We, herein, describe clinicopathologic and molecular features of a novel sinonasal sarcoma characterized by undifferentiated spindle/round cell morphology and defined by recurrent EWSR1::COLCA2 fusions. All patients (n=5) were adults (3 female and 2 male) with a median age of 46 years (range, 23 to 60 y). The tumors originated in different subsites of the sinonasal tract with frequent multisite involvement. Original diagnoses were undifferentiated or unclassified round cell/spindle cell neoplasm/sarcoma (n=4) and neuroendocrine carcinoma (n=1). Surgery with or without adjuvant chemoradiation was the treatment in all cases. At the last follow-up, 1 patient developed multiple local recurrences over 21 years and another developed local recurrence and distant metastasis to bone 27 months after diagnosis. A third patient developed local recurrence 11 months later. Two patients were disease-free at 23, and 24 months. Histology showed nondescript highly cellular neoplasms with an admixture of spindled and round cells disposed into solid sheets and fascicles with brisk mitotic activity. Immunohistochemistry was negative for all lineage-specific markers with only limited focal membranous CD99 (4 of 5 cases) and weak pankeratin (1 of 5 cases) expression. Targeted RNA sequencing revealed an EWSR1::COLCA2 fusion, verified by EWSR1 fluorescence in situ hybridization, in all cases. This series identifies a novel member in the undifferentiated spindle/round cell sarcoma category with strong predilection for the sinonasal tract. None of10,000 epithelial and mesenchymal neoplasms tested at the authors' centers during the same period showed this fusion, highlighting rarity of tumors carrying this gene fusion. Accordingly, molecular testing of unclassified sinonasal malignancies/sarcomas showing round and spindle cell morphology is recommended to enhance the identification and further characterization of this entity.
- Published
- 2022
46. SWI/SNF-deficient Sinonasal Carcinomas
- Author
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Abbas Agaimy
- Subjects
Anatomy ,Pathology and Forensic Medicine - Abstract
The classification of poorly differentiated sinonasal carcinomas and their nonepithelial mimics has experienced tremendous developments during the last 2 decades. These recent developments paved the way for an increasingly adopted approach to a molecular-based or etiology-based refined classification of the many carcinoma variants that have been historically lumped into the sinonasal undifferentiated carcinoma category. Among these new achievements, recognition of carcinoma subtypes driven by defects in the Switch/Sucrose nonfermentable (SWI/SNF) chromatin remodeling complex represents a major highlight. This resulted in a new definition of 4 sinonasal entities driven solely or predominantly by Switch/Sucrose nonfermentable complex deficiency: (1) SMARCB1(INI1)-deficient sinonasal carcinoma (lacking gland formation and frequently displaying a non-descript basaloid, and less frequently eosinophilic/oncocytoid morphology, but no features of other definable subtypes), (2) SMARCB1-deficient sinonasal adenocarcinoma (with unequivocal glands or yolk sac-like pattern), (3) SMARCA4-deficient undifferentiated (sinonasal undifferentiated carcinoma-like) carcinoma (lacking glandular or squamous immunophenotypes), and (4) SMARCA4-deficient subset (~80%) of sinonasal teratocarcinosarcoma. Fortunately, diagnostic loss of all these proteins can be detected by routine immunohistochemistry, so that genetic testing is not mandatory in routine practice. This review summarizes the main demographic, clinicopathological, and molecular features of these new entities.
- Published
- 2022
47. Guiding Individualized Patient' Care: Emerging Roles of Pathology in the Era of Immune-oncological Therapy
- Author
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Abbas Agaimy and Mahul B. Amin
- Subjects
Anatomy ,Pathology and Forensic Medicine - Published
- 2022
48. Proposal of a T3 Subclassification for Colon Carcinoma
- Author
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Susanne Merkel, Maximilian Brunner, Carol-Immanuel Geppert, Robert Grützmann, Klaus Weber, and Abbas Agaimy
- Subjects
Cancer Research ,Oncology ,colon carcinoma ,pT3 ,T3 subdivision ,distant metastasis ,survival ,prognosis ,prognostic factor ,TNM classification - Abstract
The TNM classification system is one of the most important factors determining prognosis for cancer patients. In colorectal cancer, the T category reflects the depth of tumor invasion. T3 is defined by a tumor that invades through the muscularis propria into pericolorectal tissues. The data of 1047 patients with complete mesocolic excision were analyzed. The depth of invasion beyond the outer border of the muscularis propria into the subserosa or into nonperitonealized pericolic tissue was measured and categorized in 655 pT3 patients: pT3a (≤1 mm), pT3b,c (>1–15 mm) and pT3d (>15 mm). The prognosis of these categories was compared. Five-year distant metastasis increased significantly from pT3a (5.7%) over pT3b,c (17.7%) to pT3d (37.2%; p = 0.001). There was no difference between pT2 (5.3%) and pT3a or between pT3d and pT4a (42.1%) or pT4b (33.7%). The 5-year disease-free survival decreased significantly from pT3a (77.4%) over pT3b,c (65.4%) to pT3d (50.1%; p = 0.015). No significant difference was found between pT2 (80.5%) and pT3a or between pT3d and pT4a (43.9%; p = 0.296) or pT4b (53.4%). The prognostic inhomogeneity in pT3 colon carcinoma has been demonstrated. A three-level subdivision of T3 for colon carcinoma in the TNM system into T3a (≤1 mm), T3b (>1–15 mm), and T3c (>15 mm) is recommended.
- Published
- 2022
- Full Text
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49. Recurrent IDH2 Mutations in Salivary Gland Striated Duct Adenoma Define an Expanded Histologic Spectrum Distinct From Canalicular Adenoma
- Author
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Lisa M. Rooper, Abbas Agaimy, Adel Assaad, Munita Bal, Henrietta Eugene, Jeffrey Gagan, Hiro Nonogaki, Doreen N. Palsgrove, Akeesha Shah, Edward Stelow, Robert Stoehr, Lester D.R. Thompson, Ilan Weinreb, and Justin A. Bishop
- Subjects
Surgery ,Anatomy ,Pathology and Forensic Medicine - Abstract
Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification. We identified 10 SDA and 2 tumors called low-grade adenocarcinoma not otherwise specified that were retrospectively recognized to resemble SDA. All cases showed recurrent histologic features including (1) discrete monophasic tubules, (2) tall columnar eosinophilic cells, (3) monotonous oval nuclei, and (4) scant fibrous stroma, and most were positive for S100 protein (91%), SOX10 (80%), and CK7 (80%). Although 1 case was previously called adenocarcinoma based on interdigitation with normal acini, this pattern was also seen in some SDA, and likely does not indicate malignancy; the significance of growth surrounding nerve in 1 other case is less clear. Targeted sequencing identified IDH2 R172X mutations in all 8 cases with sufficient tissue, with positivity for IDH1/2 mutation-specific immunohistochemistry in 9 cases stained. In contrast, 5 canalicular adenomas lacked IDH2 mutations or other oncogenic alterations. Overall, IDH2 R172X mutations are a defining feature of SDA that, in combination with its recognizable pathologic profile, confirm it is a unique entity separate from canalicular adenoma. IDH1/2 mutation-specific immunohistochemistry may provide a convenient tool to facilitate diagnosis. Both morphology and IDH2 mutations raise parallels between SDA and breast tall cell carcinoma with reverse polarity.
- Published
- 2022
50. Exceptional response to neoadjuvant targeted therapy with the selective RET inhibitor selpercatinib in RET-fusion-associated sarcoma
- Author
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Karin G. Schrenk, Wolfram Weschenfelder, Christian Spiegel, Abbas Agaimy, Robert Stöhr, Arndt Hartmann, Nikolaus Gaßler, Robert Drescher, Martin Freesmeyer, Amer Malouhi, Florian Bürckenmeyer, René Aschenbach, Ulf Teichgräber, Christine Kögler, Matthias Vogt, Gunther O. Hofmann, and Andreas Hochhaus
- Subjects
Cancer Research ,Oncology ,General Medicine - Abstract
With the increasing use of next-generation sequencing, highly effective targeted therapies have been emerging as treatment options for several cancer types. Recurrent gene-fusions have been recognized in sarcomas; however, options for targeted therapy remain scarce. Here, we describe a case of a sarcoma, associated with a RET::TRIM33-fusion gene with an exceptional response to a neoadjuvant therapy with the selective RET inhibitor selpercatinib. Resected tumor revealed subtotal histopathologic response. This is the first report of successful targeted therapy with selpercatinib in RET-fusion-associated sarcomas. As new targeted therapies are under development, similar treatment options may become available for sarcoma patients.
- Published
- 2022
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