- Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review
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Eric Eunshik Kim, Chul-Kee Park, Koung Mi Kang, Yoonjin Kwak, Sung-Hye Park, Jae-Kyung Won
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J Pathol Transl Med. 2024;58(3):141-145. Published online May 14, 2024
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DOI: https://doi.org/10.4132/jptm.2024.04.12
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- An aggressive subtype of inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma occurs primarily inside the abdominal cavity, followed by a pulmonary localization. Most harbor anaplastic lymphoma kinase (ALK) gene rearrangements, with RANBP2 and RRBP1 among the well-documented fusion partners. We report the second case of primary epithelioid inflammatory myofibroblastic sarcoma of the brain, with a well-known EML4::ALK fusion. The case is notable for its intra-axial presentation that clinico-radiologically mimicked glioma.
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- Inflammatory Myofibroblastic Tumor: An Updated Review
Joon Hyuk Choi Cancers.2025; 17(8): 1327. CrossRef
- The prognostic significance of p16 expression pattern in diffuse gliomas
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Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park
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J Pathol Transl Med. 2021;55(2):102-111. Published online December 23, 2020
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DOI: https://doi.org/10.4132/jptm.2020.10.22
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Abstract
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- Background
CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.
Methods p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.
Results A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).
Conclusions This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.
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Chun Wang, Cuimin Chen, Wenting Hu, Lili Tao, Jiakang Chen Apoptosis.2024; 29(3-4): 460. CrossRef - FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma
Sofian Al Shboul, Shelagh Boyle, Ashita Singh, Tareq Saleh, Moath Alrjoub, Ola Abu Al Karsaneh, Amel Mryyian, Rand Dawoud, Sinem Gul, Shaden Abu Baker, Kathryn Ball, Ted Hupp, Paul M. Brennan Brain Tumor Pathology.2024; 41(1): 4. CrossRef - p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?
Roberto Gallus, Davide Rizzo, Giorgia Rossi, Luca Mureddu, Jacopo Galli, Alberto Artuso, Francesco Bussu Pathogens.2024; 13(2): 100. CrossRef - CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization
Manali Ranade, Sridhar Epari, Omshree Shetty, Sandeep Dhanavade, Sheetal Chavan, Ayushi Sahay, Arpita Sahu, Prakash Shetty, Aliasgar Moiyadi, Vikash Singh, Archya Dasgupta, Abhishek Chatterjee, Sadhana Kannan, Tejpal Gupta Journal of Neuro-Oncology.2024; 167(1): 189. CrossRef - Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting CDKN2A/B status
Kira Tosefsky, Karina Chornenka Martin, Alexander D Rebchuk, Justin Z Wang, Farshad Nassiri, Amy Lum, Gelareh Zadeh, Serge Makarenko, Stephen Yip Neuro-Oncology Advances.2024;[Epub] CrossRef - Insights into brain tumor diagnosis: exploring in situ hybridization techniques
E. D. Namiot, G. M. Zembatov, P. P. Tregub Frontiers in Neurology.2024;[Epub] CrossRef - CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas
Sang Hyuk Lee, Tae Gyu Kim, Kyeong Hwa Ryu, Seok Hyun Kim, Young Zoon Kim Biomedicines.2024; 12(10): 2256. CrossRef - Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing
Darius Noack, Johannes Wach, Alonso Barrantes-Freer, Nils H. Nicolay, Erdem Güresir, Clemens Seidel Acta Neuropathologica Communications.2024;[Epub] CrossRef - p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances
Lucas Geyer, Thibaut Wolf, Marie-Pierre Chenard, Helene Cebula, Roland Schott, Georges Noel, Eric Guerin, Erwan Pencreach, Damien Reita, Natacha Entz-Werlé, Benoît Lhermitte Cancers.2023; 15(5): 1512. CrossRef - P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas
Meenakshi Vij, Benjamin B. Cho, Raquel T. Yokoda, Omid Rashidipour, Melissa Umphlett, Timothy E. Richardson, Nadejda M. Tsankova Acta Neuropathologica Communications.2023;[Epub] CrossRef -
CDKN2A mutations have equivalent prognostic significance to homozygous deletion in IDH-mutant astrocytoma
Raquel T Yokoda, William S Cobb, Raymund L Yong, John F Crary, Mariano S Viapiano, Jamie M Walker, Melissa Umphlett, Nadejda M Tsankova, Timothy E Richardson Journal of Neuropathology & Experimental Neurology.2023; 82(10): 845. CrossRef - Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning
Gi Jeong Kim, Tonghyun Lee, Sangjeong Ahn, Youngjung Uh, Se Hoon Kim npj Precision Oncology.2023;[Epub] CrossRef - The Prognostic Significance of P16 Immunohistochemical Expression Pattern in Women with Invasive Ductal Breast Carcinoma
Alireza Rezaei, Navidreza Shayan, Saman Shirazinia, Sara Mollazadeh, Negin Ghiyasi-Moghaddam Reports of Biochemistry and Molecular Biology.2023; 12(1): 83. CrossRef - Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park Laboratory Investigation.2022; 102(2): 160. CrossRef - Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification
Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga World Journal of Clinical Oncology.2022; 13(7): 567. CrossRef - P16INK4A—More Than a Senescence Marker
Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner Life.2022; 12(9): 1332. CrossRef
- Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach
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Seong-Ik Kim, Yujin Lee, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
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J Pathol Transl Med. 2018;52(1):28-36. Published online September 29, 2017
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DOI: https://doi.org/10.4132/jptm.2017.09.25
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Abstract
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- Background
Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients.
Methods Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups.
Results We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old).
Conclusions Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.
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- SNUH methylation classifier for CNS tumors
Kwanghoon Lee, Jaemin Jeon, Jin Woo Park, Suwan Yu, Jae-Kyung Won, Kwangsoo Kim, Chul-Kee Park, Sung-Hye Park Clinical Epigenetics.2025;[Epub] CrossRef - The prognostic significance of p16 expression pattern in diffuse gliomas
Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park Journal of Pathology and Translational Medicine.2021; 55(2): 102. CrossRef - Dynamic susceptibility contrast and diffusion MR imaging identify oligodendroglioma as defined by the 2016 WHO classification for brain tumors: histogram analysis approach
Anna Latysheva, Kyrre Eeg Emblem, Petter Brandal, Einar Osland Vik-Mo, Jens Pahnke, Kjetil Røysland, John K. Hald, Andrés Server Neuroradiology.2019; 61(5): 545. CrossRef
- Molecular Testing of Brain Tumor
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Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
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J Pathol Transl Med. 2017;51(3):205-223. Published online May 12, 2017
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DOI: https://doi.org/10.4132/jptm.2017.03.08
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31,591
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1,162
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- The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.
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- Meningeal Solitary Fibrous Tumors with Delayed Extracranial Metastasis
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Nayoung Han, Hannah Kim, Soo Kee Min, Sun-Ha Paek, Chul-Kee Park, Seung-Hong Choi, U-Ri Chae, Sung-Hye Park
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J Pathol Transl Med. 2016;50(2):113-121. Published online December 14, 2015
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DOI: https://doi.org/10.4132/jptm.2015.10.30
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Abstract
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- Background
The term solitary fibrous tumor (SFT) is preferred over meningeal hemangiopericytoma (HPC), because NAB2-STAT6 gene fusion has been observed in both intracranial and extracranial HPCs. HPCs are now considered cellular variants of SFTs. Methods: This study analyzes 19 patients with STAT6-confirmed SFTs, who were followed for over 11 years in a single institution. Ten patients (10/19, 56.2%) had extracranial metastases (metastatic group), while the remainder (9/19) did not (non-metastatic group). These two groups were compared clinicopathologically. Results: In the metastatic group, the primary metastatic sites were the lungs (n = 6), bone (n = 4), and liver (n = 3). There was a mean lag time of 14.2 years between the diagnosis of the initial meningeal tumor to that of systemic metastasis. The median age at initial tumor onset was 37.1 years in the metastatic group and 52.5 in the non-metastatic group. The 10-year survival rates of the metastatic- and non-metastatic groups were 100% and 33%, respectively. The significant prognostic factors for poor outcomes on univariate analysis included advanced age (≥45 years) and large initial tumor size (≥5 cm). In contrast, the patients with higher tumor grade, high mitotic rate (≥5/10 high-power fields), high Ki-67 index (≥5%), and the presence of necrosis or CD34 positivity showed tendency of poor prognosis but these parameters were not statistically significant poor prognostic markers. Conclusions: Among patients with SFTs, younger patients (<45 years) experienced longer survival times and paradoxically had more frequent extracranial metastases after long latent periods than did older patients. Therefore, young patients with SFTs require careful surveillance and follow-up for early detection of systemic metastases.
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Citations
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- Meningeal Solitary Fibrous Tumor: A Single-Center Retrospective Cohort Study
Siyer Roohani, Yasemin Alberti, Maximilian Mirwald, Felix Ehret, Carmen Stromberger, Soleiman Fabris Roohani, Katja Bender, Anne Flörcken, Sven Märdian, Daniel Zips, David Kaul, Manish Charan Sarcoma.2024; 2024: 1. CrossRef - De-differentiation associated with drop metastasis of a recurrent intracranial solitary fibrous tumor: a case report and literature review
Chenhui Zhao, Xiran Fan, Wanwan Gao, Fan Zhang, Haijun Lv, Xiaochun Jiang, Guangfu Di International Journal of Neuroscience.2022; 132(8): 843. CrossRef - Long-term extracranial metastatic relapse of an intraventricular solitary fibrous tumor: a case report
Tarek Assi, Elie Samaha, Hussein Nassereddine Anti-Cancer Drugs.2022; 33(1): e764. CrossRef - Multidisciplinary Treatment of Liver Metastases from Intracranial SFTs/HPCs: A Report of Three Consecutive Cases
Felix J. Krendl, Franka Messner, Gregor Laimer, Angela Djanani, Andreas Seeber, Georg Oberhuber, Dietmar Öfner, Dominik Wolf, Stefan Schneeberger, Reto Bale, Christian Margreiter Current Oncology.2022; 29(11): 8720. CrossRef - A review of solitary fibrous tumor/hemangiopericytoma tumor and a comparison of risk factors for recurrence, metastases, and death among patients with spinal and intracranial tumors.
Enrico Giordan, Elisabetta Marton, Alexandra M. Wennberg, Angela Guerriero, Giuseppe Canova Neurosurgical Review.2021; 44(3): 1299. CrossRef - Intracranial Solitary Fibrous Tumor of the Skull Base: 2 Cases and Systematic Review of the Literature
Sricharan Gopakumar, Visish M. Srinivasan, Caroline C. Hadley, Adrish Anand, Marc Daou, Patrick J. Karas, Jacob Mandel, Shankar P. Gopinath, Akash J. Patel World Neurosurgery.2021; 149: e345. CrossRef - Hemangiopericytoma/Solitary Fibrous Tumor in the central nervous system. Experience with surgery and radiotherapy as a complementary treatment: A 10-year analysis of a heterogeneous series in a single tertiary center
Pedro Miguel González-Vargas, José Luis Thenier-Villa, Pablo Sanromán Álvarez, Alexandre Serantes Combo, Lourdes Calero Félix, Raúl Alejandro Galárraga Campoverde, Eva Azevedo González, Álvaro Martín-Gallego, Rosa Martínez-Rolan, Adolfo de la Lama Zaragoz Neurocirugía.2020; 31(1): 14. CrossRef - Hemangiopericytoma/Solitary Fibrous Tumor in the central nervous system. Experience with surgery and radiotherapy as a complementary treatment: A 10-year analysis of a heterogeneous series in a single tertiary center
Pedro Miguel González-Vargas, José Luis Thenier-Villa, Pablo Sanromán Álvarez, Alexandre Serantes Combo, Lourdes Calero Félix, Raúl Alejandro Galárraga Campoverde, Eva Azevedo González, Álvaro Martín-Gallego, Rosa Martínez-Rolan, Adolfo de la Lama Zaragoz Neurocirugía (English Edition).2020; 31(1): 14. CrossRef - Solitary fibrous tumor/hemangiopericytoma: treatment results based on the 2016 WHO classification
Kyoung Su Sung, Ju Hyung Moon, Eui Hyun Kim, Seok-Gu Kang, Se Hoon Kim, Chang-Ok Suh, Sun Ho Kim, Kyu-Sung Lee, Won Seok Chang, Jong Hee Chang Journal of Neurosurgery.2019; 130(2): 418. CrossRef - Grading of meningeal solitary fibrous tumors/hemangiopericytomas: analysis of the prognostic value of the Marseille Grading System in a cohort of 132 patients
Nicolas Macagno, Rob Vogels, Romain Appay, Carole Colin, Karima Mokhtari, Benno Küsters, Pieter Wesseling, Dominique Figarella‐Branger, Uta Flucke, Corinne Bouvier Brain Pathology.2019; 29(1): 18. CrossRef - Solitary fibrous tumor of the pineal region with delayed ectopic intracranial metastasis: A case report and review of the literature
Yongjie Wang, Jingying Zhang, Qichang Liu, Fuyi Liu, Xiangdong Zhu, Jianmin Zhang Medicine.2019; 98(21): e15737. CrossRef - Case report: neonatal giant forehead hemangiopericytoma with a 5-year follow-up
AiJun Peng, LiBing Zhang, Hai Zhao, LiangXue Zhou Medicine.2019; 98(47): e17888. CrossRef - Liquid Biopsy in Rare Cancers: Lessons from Hemangiopericytoma
Chiara Nicolazzo, Luciano Colangelo, Alessandro Corsi, Guido Carpino, Angela Gradilone, Chiara Sonato, Cristina Raimondi, Eugenio Gaudio, Paola Gazzaniga, Walter Gianni Analytical Cellular Pathology.2018; 2018: 1. CrossRef - Surveillance for metastatic hemangiopericytoma-solitary fibrous tumors-systematic literature review on incidence, predictors and diagnosis of extra-cranial disease
Tarini Ratneswaren, Florence Rosie Avila Hogg, Mathew Joseph Gallagher, Keyoumars Ashkan Journal of Neuro-Oncology.2018; 138(3): 447. CrossRef - Intracranial Solitary Fibrous Tumor
Eveline Claus, Patrick Seynaeve, Jeroen Ceuppens, Alain Vanneste, Koenraad Verstraete Journal of the Belgian Society of Radiology.2017;[Epub] CrossRef - Comparison and evaluation of risk factors for meningeal, pleural, and extrapleural solitary fibrous tumors: A clinicopathological study of 92 cases confirmed by STAT6 immunohistochemical staining
Ji Min Kim, Yoon-La Choi, Yu Jin Kim, Hyung Kyu Park Pathology - Research and Practice.2017; 213(6): 619. CrossRef - Molecular Testing of Brain Tumor
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi Journal of Pathology and Translational Medicine.2017; 51(3): 205. CrossRef - Solitary fibrous tumour presenting with a single bone metastasis: report of six cases and literature review
Vittoria Colia, Salvatore Provenzano, Carlo Morosi, Paola Collini, Salvatore Lorenzo Renne, Paolo G. Dagrada, Claudia Sangalli, Angelo Paolo Dei Tos, Andrea Marrari, Paolo G. Casali, Silvia Stacchiotti Clinical Sarcoma Research.2016;[Epub] CrossRef
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