1. Overdiagnosis of atypical lipomatous tumors/well-differentiated liposarcomas by morphological diagnosis using only HE stained specimens: a case-control study with MDM2/CDK4 immunostaining and MDM2/CDK4 fluorescence in situ hybridization.
- Author
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Nomura K, Tomita M, Kuroda K, Souda M, Chiba K, Yonekura A, and Osaki M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Adult, Case-Control Studies, Aged, 80 and over, Immunohistochemistry, Diagnosis, Differential, Biomarkers, Tumor metabolism, Proto-Oncogene Proteins c-mdm2 metabolism, Proto-Oncogene Proteins c-mdm2 genetics, Cyclin-Dependent Kinase 4 metabolism, Cyclin-Dependent Kinase 4 genetics, In Situ Hybridization, Fluorescence, Liposarcoma diagnosis, Liposarcoma metabolism, Liposarcoma genetics, Liposarcoma pathology, Lipoma diagnosis, Lipoma metabolism, Lipoma pathology, Lipoma genetics
- Abstract
Background: Lipomatous tumors represent the most common type of soft tissue neoplasms. Mouse double minute 2 homolog (MDM2)/cyclin-dependent kinase 4 (CDK4) immunostaining is considered effective in differentiating between benign lipomas and intermediate malignant atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLPSs). However, these tumors have traditionally been diagnosed histopathologically using hematoxylin and eosin-stained specimens, which is referred to here as morphological diagnosis. In this study, the accuracy of morphological diagnoses that had been made before MDM2/CDK4 immunostaining became available for distinguishing between lipoma and ALT/WDLPS was examined., Methods: The study participants were 109 patients with a morphological diagnosis of lipoma (68 patients) or ALT/WDLPS (41 patients) who had undergone surgical resection of the tumor in our hospital between 2009 and 2012. Tissue samples from all patients were used for MDM2/CDK4 immunostaining and the confirmation of MDM2/CDK4 amplification by fluorescence in situ hybridization (FISH)., Results: Of the 41 patients with a morphological diagnosis of ALT/WDLPS, only 17 were positive for MDM2 FISH. In addition, one of the 68 patients with a morphological diagnosis of lipoma showed MDM2 amplification by FISH. When the definitive diagnosis of ALT/WDLPS was made by the positive results of MDM2 FISH, the sensitivity and specificity of morphological diagnosis were 41.5% and 98.5%, respectively. The sensitivity of MDM2 and CDK4 immunostaining was 55.6% and 40.0%, respectively, and their specificity was 87.0% and 84.6%, respectively. This indicates that the diagnostic accuracy of these immunostaining assays was not particularly high. The clinical features suggesting ALT/WDLPS were: patient age (older), maximum tumor diameter (large, cut-off value of 125 mm), tumor location (lower limb), and tumor depth (deep-seated)., Conclusions: Morphological diagnosis alone can accurately diagnose lipomas. However, it has a propensity to overdiagnose ALT/WDLPS. Thus, MDM2 FISH should be used more proactively, not only for lesions with obvious morphological abnormalities, but also for lipomatous tumors that are clinically suggestive of ALT/WDLPS., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Committee of Nagasaki University Hospital (Approval Number: 17061909–3). Written informed consent was waived by this committee for this retrospective analysis of routinely acquired imaging and clinical data. The outline of this research was published on the homepage of the Clinical Research Center of Nagasaki University Hospital. This guaranteed the patients and any other individuals the opportunity to refuse participation in the study. We did not receive any refusion of participation. Each author certifies that all investigations were conducted in conformity with the ethical principles of research. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
- Published
- 2024
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