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
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/...
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BMC
2024-11-01
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| Online Access: | https://doi.org/10.1186/s12885-024-13215-4 |
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| author | Kentaro Nomura Masato Tomita Kishio Kuroda Masakazu Souda Ko Chiba Akihiko Yonekura Makoto Osaki |
| author_facet | Kentaro Nomura Masato Tomita Kishio Kuroda Masakazu Souda Ko Chiba Akihiko Yonekura Makoto Osaki |
| author_sort | Kentaro Nomura |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-d1e00e48e5754eb493793f6fbda2f8ba2025-08-20T02:22:26ZengBMCBMC Cancer1471-24072024-11-012411910.1186/s12885-024-13215-4Overdiagnosis 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 hybridizationKentaro Nomura0Masato Tomita1Kishio Kuroda2Masakazu Souda3Ko Chiba4Akihiko Yonekura5Makoto Osaki6Department of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical SciencesDepartment of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical SciencesDepartment of Pathology Informatics, Nagasaki University Graduate School of Biomedical SciencesCancer Genomic Unit Clinical Genome Center, Nagasaki University HospitalDepartment of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical SciencesDepartment of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical SciencesDepartment of Orthopaedic Surgery, Nagasaki University Graduate School of Biomedical SciencesAbstract 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.https://doi.org/10.1186/s12885-024-13215-4Atypical lipomatous tumorLipomaFISHImmunohistochemistryMDM2CDK4 |
| spellingShingle | Kentaro Nomura Masato Tomita Kishio Kuroda Masakazu Souda Ko Chiba Akihiko Yonekura Makoto Osaki 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 BMC Cancer Atypical lipomatous tumor Lipoma FISH Immunohistochemistry MDM2 CDK4 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Atypical lipomatous tumor Lipoma FISH Immunohistochemistry MDM2 CDK4 |
| url | https://doi.org/10.1186/s12885-024-13215-4 |
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