Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis

Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis Kana Sugiyama, Kota Washimi, Shinya Sato, Toru Hiruma, Mai Sakai, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-900482/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Jan, 2022 Read the published version in Diagnostic Cytopathology → Version 1 posted You are reading this latest preprint version Abstract Background: Adipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL) comprising the majority of cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL. Methods: Fluorescence in situ hybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog ( MDM2 ) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Papanicolaou, and evaluated for 12 cytological parameters by six cytotechnologists. Results: The findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with MDM 2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in the lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%), and therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting the diagnosis of ALT/WDL. FISH of MDM2 on Papanicolaou-stained specimens was performed in four cases. In two cases, the results were similar to those of MDM2 FISH performed on FFPE sections and were reproducible, whereas in two other cases, the signal could not be evaluated because of the strong background coloration. Conclusions: Cytology specimens may be useful for preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Papanicolaou-stained specimens and the detection accuracy of MDM2 amplification can be improved. Pathology Cytology Lipoma Well-differentiated liposarcoma Fluorescence in situ hybridization MDM2 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Background Adipocytic tumors are the most common soft tissue tumors and mostly comprise lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL). ALT/WDL can become highly malignant by dedifferentiation or recurrence, thereby making it important to differentiate them from lipomas, which are benign tumors, for appropriate treatment and for determining the follow-up period after tumor resection. 1 The mouse double minute 2 homolog (MDM2) protein suppressively regulates TP53 , a tumor suppressor gene. Fluorescence in situ hybridization (FISH) analysis of formalin-fixed paraffin-embedded (FFPE) tissues has revealed MDM2 amplification in ALT/WDL and is currently used to differentiate these tumors. 2 – 4 With the development of new molecular tests showing high diagnostic specificity, fine-needle aspiration cytology (FNAC) has begun to gain acceptance for preoperative assessment of soft tissue tumors. 5 FNAC represents a versatile, low-cost, well-tolerated diagnostic strategy with obvious advantages over histological biopsies. 6 However, a detailed comparison of the cytological findings of lipoma and ALT/WDL with MDM2 amplification has not yet been reported. In this study, we compared the cytological features of lipoma and ALT/WDL and used the cytological findings for their differential diagnosis. We also performed FISH to examine MDM2 amplification in cytological specimens and to evaluate the usefulness of cytology for differential diagnosis of adipocytic tumors. Materials And Methods We reviewed the clinical and histological data of 20 patients with lipoma and ALT/WDL who had undergone resection at Kanagawa Cancer Center between 2018 and 2020. One ALT/WDL case showed partially dedifferentiated areas. We evaluated age, sex, and maximum tumor diameter as the clinical parameters. As cytological specimens, tissue samples (2–3 mm in size) were randomly collected from the center of the surgical specimens, mimicking FNAC, and subjected to Papanicolaou staining. If the case showed a dedifferentiated area, the sample was collected from the ALT/WDL area. Six cytotechnologists (CTs) evaluated the cell morphology, number of lipoblasts, size of adipocytes, nuclear pleomorphism, intranuclear vacuoles, multinucleated cells, nuclear enlargement, unequal size of nuclei, irregular nuclear borders, hyperchromatosis, prominent nucleoli, large atypical cells, and background necrosis (Fig. 1 a–g). Large atypical cells were defined as cells with increased chromatin and irregular nuclear enlargement (Fig. 1 h–l). The morphology of each cell was evaluated on a score of 4 (1: almost none, 2: a little, 3: common, 4: prominent), and background necrosis was assessed on a score of 2 (0: absent, 1: present). Furthermore, each CT estimated the histological type of the lipoma or ALT/WDL based on the cytological findings. More than 200 cells were examined using a WinROOF2018 image analyzer (MITANI Corporation, Tokyo, Japan), and the short nuclear diameter was measured for samples subjected to Papanicolaou staining. The FFPE blocks of the surgical samples were prepared for histological examination. Resected specimens were fixed in 10% neutral-buffered formalin. At least one block per centimeter of the largest diameter of the tumor was prepared for histological evaluation. If the maximum diameter was 10 cm, more than 10 FFPE blocks were prepared for histological evaluation. The two pathologists evaluated nuclear atypia of adipocytes and atypical stromal cells and made a histological diagnosis. Immunostaining for MDM2 and CDK4 and FISH examination for MDM2 were performed in all cases using FFPE specimens. In addition, in four cases, FISH for MDM2 was performed using Papanicolaou-stained specimens. The histological type determined by at least four of six CTs was used as the cytological diagnosis result for analysis. We used the Mann–Whitney U test to analyze the association between the clinical findings, histological diagnosis, cytological diagnosis, and the length of the short diameter of the cell nuclei and the presence of MDM2 amplification. We analyzed the association between each cytological finding and each diagnosis based on Papanicolaou-stained specimens using Spearman’s correlation and then examined the mean values. We also analyzed the association between the total score of the cytological findings of the six CTs and the presence of MDM2 amplification using Spearman’s correlation. Statistical analysis was performed using SPSS version 26 software (SPSS Inc., Chicago, IL, USA). Results with p < 0.05 were considered statistically significant. Immunohistochemistry Deparaffinized tumor sections were stained for CDK4 (Clone DCS-31, Thermo Fisher Scientific, Waltham, MA, USA) and MDM2 (Clone IF2, Thermo Fisher Scientific) using the heat-induced epitope retrieval method. Appropriate positive and negative controls were used in all analyses. Immunostaining was evaluated based on the intensity and proportion of tumor cell staining in each specimen. The intensity of staining was defined by applying Allred scoring 7 as follows: 3+, strong; 2+, moderate; 1+, weak; −, no staining. The proportion of staining was measured for each specimen and classified by applying Allred scoring as follows: 5, > 66%; 4, 66–33%; 3, 33–10%; 2, 10–1%; 1, < 1%; 0, 0%. Cases were defined as MDM2-positive if the Allred score of the marker (defined as the combined value of the intensity score and proportion score) was more than 1. Moreover, cases were considered as CDK4-positive if the Allred score of the marker was more than 5. FISH analysis FISH for MDM2 was performed in all 20 cases using FFPE tissues with the Vysis®ฎ LSI®ฎ MDM2 SpectrumOrange Probe (CEP®ฎ 12 [D12Z3], Abbott Molecular, Des Plaines, IL, USA) according to the manufacturer’s protocol. The probe cocktail decorates the human chromosomal region harboring MDM2 with an orange signal and the centromeric region of chromosome 12 with a green signal. The signals were scored by counting a minimum of 20 non-overlapping nuclei per case, and the average of MDM2 and centromere 12 signals was calculated. An MDM2 /chromosome 12 signal ratio of > 2.0 was considered to represent MDM2 amplification (amplification-positive). FISH for MDM2 was performed using the Papanicolaou-stained specimen to evaluate the cytological findings in four cases. Using FISH in FFPE samples, two cases showed MDM2 amplification whereas two cases did not. After xylene was removed using 100% ethanol, the samples were destained with ethanol hydrochloride for 2–3 h. Next, the samples were washed with 100% ethanol and incubated overnight at room temperature (20–30°C). The specimens were immersed in 0.2% hydrochloride for 20 min, followed by immersion in distilled water for 1 min, a wash buffer for 5 min, and finally protease solution (Abbott Molecular; pre-warmed to 37°C ± 1°C) for 10 min. Samples were again immersed in wash buffer for 5 min, and the procedure was repeated. Next, the samples were immersed in 10% neutral-buffered formalin for 10 min followed by immersion in wash buffer for 5 min, and the procedure was repeated. Finally, the Vysis®ฎ LSI®ฎ MDM2 SpectrumOrange Probe was added to the denatured DNA, and hybridization was carried out at 73°C for 3 min, followed by overnight incubation at 37°C. The cells were washed to eliminate non-specific signals by immersing them in hybridization wash buffer (2X SSC/0.3% NP-40; Abbott Molecular) preheated to 72°C ± 1°C for 2 min. The specimens were immersed in wash buffer and DAPI was added, followed by observation with fluorescence microscope Ti-E equipped with a Triple Bandpass Filter Set, DAPI/Green/Orange v2 (Nikon Corporation, Tokyo, Japan). Results The participants included 13 men and 7 women, with a mean age of 56 years. The most commonly affected site was the thigh (n = 10), and the mean maximum tumor diameter was 133 mm. Seven cases were histologically diagnosed as lipoma and 13 cases as ALT/WDL. The mean nucleus short diameter of tumor cells measured from the Papanicolaou-stained samples was 4.02 µm, with a median of 3.75 µm. The short diameter of the nucleus in most tumor cells observed in Papanicolaou-stained samples was less than 5 µm, and a few tumor cells had nuclei with a short diameter of more than 10 µm. Immunostaining evaluation using FFPE tissues revealed 9 MDM2-positive cases and 11 CDK4-positive cases. In 12 cases, MDM2 amplification was observed by performing FISH on FFPE tissues (Table 1 ). Table 1 Clinicopathological findings of patients with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas. (min, max) Male/Female, n 13/7 Age, years † 56 ± 15 (19, 90) Tumor size, mm † 133 ± 73 (50, 350) Location, n Thigh 10 Neck 3 Head 1 Buttocks 1 Foot 1 Inguinal region 1 Lower leg 1 Upper arm 1 Retroperitoneum 1 Histological diagnosis Lipoma 7 ALT/WDL 13 Nucleus short diameter, µm † Average 4.02 ± 0.53 (3.26, 5.03) (Papanicolaou staining) Maximum diameter 10.07 ± 2.62 (6.21, 14.82) Proportion of nucleus diameter, % † ≥ 5 µm 20.4 ± 10.8 (3.4, 38.2) (Papanicolaou staining) ≥ 6 µm 9.6 ± 7.7 (0.5, 24.8) ≥ 7 µm 4.9 ± 5.0 (0, 18.3) ≥ 8 µm 2.3 ± 2.8 (0, 9.2) ≥ 9 µm 1.1 ± 1.5 (0, 4.2) ≥ 10 µm 0.6 ± 0.9 (0, 2.9) MDM2 FISH (20 cells) ‡ MDM2 signals total 168.5 (33–230) (28, 449) MDM2/CEP®12 ratio 4.95 (0.98–6.70) (0.8, 13.6) Amplification +/− 12/8 †values are the means ± SD (min, max). ‡values are the median (interquartile range). ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; FISH, fluorescence in situ hybridization. In nine cases, at least four out of six CTs predicted ALT/WDL based on the cytological characteristics of the Papanicolaou-stained tissue samples. Moreover, MDM2 amplification was observed by FISH in each of these nine cases. The nucleus short diameter was significantly longer (p < 0.001), with a larger standard deviation in cases with MDM2 amplification, indicating greater variation in the nuclear size. Cells in which the short diameter of the nucleus was greater than 9 µm were not observed in cases in which MDM2 was not amplified (Table 2 ). Table 2 Association between clinical findings, immunostaining results, and the length of the short diameter of cell nuclei in cases with and without MDM2 amplification detected by FISH. MDM2 amplification (+) MDM2 amplification (−) p -value 12 cases 8 cases MDM2 signal (20 cells) § 247.7 ± 89.6 31.9 ± 2.1 CEP signal (20 cells) § 36.0 ± 8.3 33.6 ± 2.9 MDM2 / CEP12 ratio § 7.24 ± 3.02 0.95 ± 0.1 Percentage of cells with MDM2 / CEP12 ratio > 2.0 § 80.8 ± 10.4 0 ± 0 Male/Female, n 8 / 4 5 / 3 0.910 Age, years § 58 ± 15 51 ± 15 0.427 Tumor size, mm § 156 ± 80 97 ± 44 0.082 Histologic specimen Histological diagnosis ALT/WDL, cases 12 1 < 0.001 Immunohistochemistry MDM2 9 0 0.004 positive cases † CDK4 11 0 < 0.001 Cytologic specimen Cytological diagnosis ALT/WDL, cases ‡ 9 0 0.004 Nucleus short diameter, µm § Average 4.32 ± 0.44 3.57 ± 0.29 < 0.001 SD 1.61 ± 0.30 1.11 ± 0.15 Maximum diameter 11.6 ± 2.2 7.76 ± 0.87 Proportion of nucleus diameter, % § ≧ 5 µm 26.4 ± 9.2 11.3 ± 5.4 0.001 ≧ 6 µm 14.0 ± 7.2 3.4 ± 2.3 < 0.001 ≧ 7 µm 7.4 ± 5.0 1.1 ± 1.0 < 0.001 ≧ 8 µm 3.6 ± 3.0 0.3 ± 0.3 0.001 ≧ 9 µm 1.9 ± 1.5 0 ± 0 0.004 ≧ 10 µm 1.0 ± 0.9 0 ± 0 0.012 †allred score MDM2: more than 1, CDK4: more than 5. ‡cases that more than half of the cytotechnologists judged as ALT/WDL. §values are the means ± SD. ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; FISH, fluorescence in situ hybridization. The six CTs identified the samples as lipoma or ALT/WDL based on the cytological findings with a concordance rate of 88.3%. The mean concordance rate of identifying samples as lipoma or ALT/WDL based on cytological and histopathological findings was 76.7% (65% minimum, 90% maximum), whereas that based on cytological findings and MDM2 amplification by FISH was 78.3% (70% minimum, 85% maximum). Cytological findings with a relatively high concordance rate among evaluation by CTs included lipoblasts, necrosis, large atypical cells, multinucleated cells, and pleomorphism. The cytological findings that correlated significantly with MDM2 amplification by FISH included pleomorphism, unequal size of adipocytes, irregular nuclear borders, hyperchromatosis, unequal size of nuclei, nuclear enlargement, prominent nucleoli, large atypical cells, and multinucleated cells. The relationship between cytological findings and ALT/WDL identification by each CT was relatively strong for pleomorphism, nuclear enlargement, and unequal nuclear size (Table 3 ). In the group with MDM2 amplification, the total scores of large atypical cells, multinucleated cells, and pleomorphism were higher. The mean total score of the above three findings was less than 5 in the group without MDM2 amplification, although some cases had total scores of less than 5 in the group with MDM2 amplification. A single CT rescreened a 1 cm 2 area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. Sixty-seven percent (8/12 cases) of the cases with MDM2 amplification had large atypical cells. No large atypical cells were found in lipoma cases (Table 4 ). Table 3 Mean concordance rate between cytological findings among cytotechnologists (CTs). Evaluation concordance rate, % † Cytological diagnosis † MDM2/CEP12 ratio r. p -value r. p -value Lipoblasts 94.9 0.204 0.432 0.312 0.181 Necrosis 90.0 0.400 0.163 0.416 0.068 Large atypical cells 73.4 0.680 0.022 0.601 0.005 Multinucleated cells 66.7 0.641 0.035 0.559 0.005 Pleomorphism 65.1 0.812 < 0.001 0.781 < 0.001 Unequal size of adipocytes 60.0 0.619 0.056 0.711 < 0.001 Irregular nuclear borders 60.0 0.712 0.051 0.694 0.001 Prominent nucleoli 57.6 0.593 0.012 0.608 0.004 Unequal size of nuclear 56.6 0.764 0.001 0.668 0.001 Nuclear enlargement 55.1 0.780 0.001 0.640 0.002 Hyperchromatosis 54.1 0.688 0.170 0.693 0.001 Intranuclear vacuoles 52.4 0.152 0.381 -0.116 0.625 Cytological diagnosis 88.3 0.693 0.001 Means determined by the six CTs were used for evaluating the association between cytological findings and each individual’s estimated histological type by Papanicolaou-stained specimens. The association between the total score of cytological findings of six CTs and the presence of MDM2 amplification is shown. †Values are the means Table 4 Results of MDM2 amplification by FISH using FFPE specimens and histological diagnosis and cytological impression. Case FISH Histological diagnosis Cytological impression † Cytological morphology Score Average (1–4) ‡ Large atypical cell re-examination § Number of MDM2 MDM2/CEP12 Large atypical cells Multinucleated cells Pleomorphism Total score 1 28 0.8 Lipoma Lipoma 1.3 1.7 1.7 4.7 0 2 30 0.9 Lipoma Lipoma 1.2 1.3 1.7 4.2 0 3 31 1.1 Lipoma Lipoma 1.2 1.2 1.2 3.6 0 4 32 0.9 Lipoma Lipoma 1 1.3 1.2 3.5 0 5 32 1.1 Lipoma Lipoma 1 1 1 3 0 6 33 0.9 Lipoma Lipoma 1 1.3 1 3.3 0 7 34 1 Liposarcoma Lipoma 1.3 1.3 1.8 4.4 0 8 35 0.9 Lipoma Lipoma 1.3 1.2 1.5 4 0 9 144 5.3 Liposarcoma Liposarcoma 2.2 2.5 2.8 7.5 4 10 156 2.6 Liposarcoma Liposarcoma 1.8 2.5 2.7 7 1 11 181 4.8 Liposarcoma Lipoma 1 1 1.3 3.3 0 12 181 6.2 Liposarcoma Lipoma 1 1.2 2.2 4.4 0 13 192 5.1 Liposarcoma Liposarcoma 2.7 2.8 3.2 8.7 1 14 220 5.9 Liposarcoma Liposarcoma 2.5 2.8 3.3 8.6 2 15 220 6.7 Liposarcoma Liposarcoma 1.7 2.2 2.2 6.1 0 16 260 6.7 Liposarcoma Lipoma 1.3 1.5 2 4.8 1 17 283 8.3 Liposarcoma Liposarcoma 1.8 2.2 2.2 6.2 0 18 301 9.7 Liposarcoma Liposarcoma 2 2.2 2.8 7 1 19 385 12 Liposarcoma Liposarcoma 1.7 2 3 6.7 3 20 449 13.6 Liposarcoma Liposarcoma 2.2 2.2 3 7.4 2 The mean value of the cytological morphology scores of six CTs. A single CT rescreened a 1 cm 2 area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. †More than four out of the six CTs’ results. ‡Average of the scores evaluated by six CTs. §A single CT rescreened a 1 cm 2 area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. FISH, fluorescence in situ hybridization; FFPE, formalin-fixed paraffin-embedded specimens. FISH examination was performed on Papanicolaou-stained specimens from two cases in which MDM2 amplification was confirmed by FISH using FFPE specimens (Table 5 , Fig. 2 ). Case 1 exhibited relatively high MDM2 signals in FFPE specimens, as well as higher signals in Papanicolaou-stained specimens, whereas case 2 exhibited relatively low MDM2 signals in FFPE specimens and lower signals in Papanicolaou-stained specimens. Signal evaluation by performing FISH on Papanicolaou-stained FFPE specimens from two cases without MDM2 amplification was difficult because of the presence of strong background signals (Fig. 3 ). Table 5 Results of FISH using FFPE and Papanicolaou-stained specimens. MDM2 † CEP12 † MDM2 / CEP12 MDM2/CEP12 > 2.0 cells (%) Case 1 FFPE 449 33 13.6 95 Papanicolaou 357 41 8.3 100 Case 2 FFPE 156 61 2.6 65 Papanicolaou 201 64 3.1 70 †Number of signals in 20 cells. FISH, Fluorescence in situ hybridization; FFPE, formalin-fixed paraffin-embedded specimens. Discussion We evaluated and compared cytological findings, MDM2 amplification, and histological diagnosis to identify patient samples either as lipoma or ALT/WDL. The concordance rate for distinguishing between these two conditions based on cytologic specimens and histological findings was 76.7%, indicating that small cytological specimens can predict the whole tissue histological findings with high probability. CTs focused on pleomorphism, nuclear enlargement, and unequal size of nucleus in predicting lipoma or ALT/WDL, but the concordance rates between CTs were low for parameters such as nuclear enlargement and nuclear size. The cytological findings with a high concordance rate among CTs were strongly associated with histology and MDM2 amplification, multinucleated cells, pleomorphism, and large atypical cells. If the sum of the scores for the multinucleated cells, pleomorphism, and large atypical cells was 3 for lipoma and 4–12 for ALT/WDL, and the MDM2 amplification indicated ALT/WDL, positive sensitivity was 90.3%, negative sensitivity was 64.6%, and the total concordance rate was 80.0%. Specimens from ALT/WDL cases, showing MDM2 amplification and all three findings with score 1, showed some multinucleated cells; detailed evaluation of these findings may increase the positive sensitivity. However, few multinucleated cells were observed in lipoma cases without MDM2 amplification. A single CT rescreened a 1-cm 2 area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. As large atypical cells were not found in the lipoma cases, it was considered a highly specific cellular finding of ALT/WDL. However, the sensitivity of large atypical cells was not high. Comprehensive evaluation of multinucleated cells and pleomorphism is important for predicting the diagnosis of ALT/WDL. MDM2 amplification may be predicted using cytological specimens with even greater probability by considering the above-mentioned three cytological findings, namely multinucleated cells, pleomorphism, and large atypical cells. In one case, the histological findings indicated ALT/WDL, and amplification of MDM2 was not observed by FISH. This case was diagnosed as ALT/WDL because of the presence of a small number of large nucleated cells. If it is difficult to identify a distinct atypical cell, MDM2 amplification by FISH must be confirmed for final diagnosis. In this case, four of six CTs presumed the sample to be a lipoma based on the cytological specimens. In a few cases of ALT/WDL, atypical cells were identified relatively easily in cytological specimens, even when it was difficult to identify atypical cells in the histological specimens (Fig. 4 ). Although tissue specimens can be examined over a wide area, cytological specimens can be used to evaluate nuclear atypia in more detail and may help improve diagnostic accuracy in combination with tissue specimens. The length of the nucleus short diameter in the Papanicolaou-stained cytological specimens was significantly greater in cases showing MDM2 amplification. Additionally, a significant difference in SD values was also observed, suggesting that unequal nuclear size was prominent in the MDM2 amplification group, which may reflect as pleomorphism in cytological findings. In cases without MDM2 amplification, few cells with a nucleus short diameter greater than 7 µm were observed, but none of the cells had a nucleus short diameter greater than 9 µm. Although most adipocytic tumors are lipoma and ALT/WDL, other adipocytic neoplasms should be included when performing differential diagnosis before surgery. These include adipocytic tumors, such as angiolipomas, myolipomas, chondrolipomas, spindle cell lipomas, pleomorphic lipomas, atypical spindle cell/pleomorphic lipomatous tumors, lipomatous myxoid liposarcomas, dedifferentiated liposarcomas, and pleomorphic liposarcomas. These tumors were not considered in the present study. Angiolipomas are generally more common among young individuals in their late teens and early 20s. 8 Myolipoma is a rare tumor that does not show atypical cells, as observed in ALT/WDL. 8 A chondroid lipoma is a rare tumor composed of relatively cohesive clusters of mature adipocytes and variably sized lipoblasts in a chondromyxoid matrix. 9 , 10 Approximately 80% of spindle cell lipomas and pleomorphic lipomas arise within the subcutaneous tissue of the posterior neck, back, and shoulders. 11 , 12 Atypical spindle cell/pleomorphic liposomal tumors in the hands and feet include mild to moderately atypical spindle cells, adipocytes, lipoblasts, and pleomorphic cells. 8 These benign adipocytic neoplasms can be differentiated from ALT/WDL by examining MDM2 amplification. Preoperative diagnosis of myxoid liposarcoma is important because preoperative radiotherapy and excision methods differ from those for ALT/WDL. Myxoid liposarcoma is more common among individuals in their 30s and 40s and tends to be less pleomorphic than ALT/WDL. Identifying DDIT3 rearrangement using FISH break-apart probes is a sensitive, specific strategy for the diagnosis of myxoid liposarcoma. 8 Dedifferentiated liposarcoma often indicates ATL/WDL around the tumor, as revealed by imaging findings. 8 Preoperative imaging findings rarely indicate pleomorphic liposarcoma as an adipocytic tumor. 13 Currently, while considering treatment strategies for adipocytic tumor, it is important to differentiate among benign lipoma, ALT/WDL with the potential for recurrence and malignancy, and myxoid liposarcoma with the potential for distant metastasis that requires wide resection. FISH examination plays an important role in differentiating among these three conditions. In the present study, the results of MDM2 amplification obtained by FISH of cytological specimens were consistent with the FISH results obtained using FFPE specimens. In two cases with no MDM2 amplification, it was difficult to detect signals by FISH using Papanicolaou-stained specimens. This may be attributed to the strong background staining. In order to avoid background signals, it is necessary to consider methods such as dividing the sample for analysis and conducting Papanicolaou staining and FISH separately. It is necessary to optimize the assay conditions to improve the accuracy of MDM2 FISH in the cytological specimens of adipocytic tumors. If FISH for DDIT3 can be performed on cytological specimens, several adipocytic tumors may be predicted from these samples (Fig. 5 ). It is possible to detect genes using small specimens, and minimally invasive FNAC may be used for preoperative diagnosis of various tumors, including soft tissue tumors. 5 In the era of genetic analysis of small tissue specimens, preoperative diagnosis by FNAC, a minimally invasive test, may play a major role in determining treatment plans. Familiarity with the cell morphology of cytological specimens derived from tumors is important for making a differential diagnosis. Preoperative diagnosis of lipoma or ALT/WDL can provide important information for deciding the treatment plan. In the future, it will be important to examine and analyze the diagnostic accuracy of cytological morphology in actual aspiration biopsy specimens. Given that the size of the patient dataset was small (n = 20), we will consider a follow-up study with a larger cohort. Our results may facilitate differential diagnoses for patients with lipoma and ALT/WDL and assist clinicians in making treatment decisions. Conclusion Lipoma or ALT/WDL can be predicted with a high probability by evaluating the cytological findings of multinucleated cells, pleomorphism, and large atypical cells in Papanicolaou-stained tissue specimens. However, it is sometimes difficult to confirm the diagnosis based only on cell morphology, and further confirmation of MDM2 amplification by FISH is important. If the accuracy of MDM2 FISH in cytological specimens can be improved, cytology may become a useful tool for the preoperative differential diagnosis of adipocytic tumors. Abbreviations ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; CTs, cytotechnologists; FFPE, formalin-fixed paraffin-embedded specimens; FISH, fluorescence in situ hybridization; FNAC, fine-needle aspiration cytology. Declarations Ethics approval and consent to participate: We applied the opt-out method to obtain patient consent for this study. This study was approved by the research ethics review committee of Kanagawa Cancer Center (approval no. 2020 epidemiology-22). Consent for publication: Not applicable Availability of data and materials: All data generated or analysed during this study are included in this published article. Competing interests: The authors declare that they have no competing interests. Funding: This research was supported by joint research funding from Kanagawa Cancer Center Hospital-Research Institute Joint Study (grant no. 2020-12) and a grant-in-aid for scientific research (grant no. JP 20K16210) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. Author contributions: KS: Evaluation of cell morphology and FISH results, immunostaining. KW: Substantial contributions to the conception and design of the work, analysis of results, histological diagnosis, and writing of the manuscript. SS: Analysis of clinicopathological findings. TH: Analysis of clinicopathological findings. MS: Evaluation of cell morphology. KK: Evaluation of cell morphology. YO: Analysis of clinicopathological findings. YM: Analysis of clinicopathological findings. TY: Analysis of clinicopathological findings, histological diagnosis. All authors read and approved the final manuscript. Acknowledgments: We are grateful to Dr. Masayuki Takagi for advice on the histological diagnosis and to the technical staff at Kanagawa Cancer Center, Mei Sawaguchi, Ryuji Nasu, Shigeko Iwanade, Tomomi Hasumoto, and Kazuhisa Kitamura, for evaluating cytological findings and their expert technical assistance. References Satoshi Nagano, Masahiro Yokouchi, Takao Setoguchi, et al. Differentiation of lipoma and atypical lipomatous tumor by a scoring system: implication of increased vascularity on pathogenesis of liposarcoma. BMC Muxculoskelet Disord. 2015; 16: 36. Sirvent N, Coindre JM, Maire G, et al. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol. 2007 Oct;31(10) :1476-1489. Creytens D, Van Gorp J, Speel EJ, Ferdinande F. Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis. Anticancer Res. 2015 Nov;84(11):2222-2230. Tap WD, Eilber FC, Ginther C, et al. Evaluation of well-differentiated/de-differentiated liposarcoma by high-resolution oligonucleotide array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2011 Feb;50(2):95-112. Francesca Pagliuca, Andrea Ronchi, Immacolata Cozzolino, Marco Montella,Federica Zito Marino,Renato Franco. Mesenchymal neoplasms: Is it time for cytology? New perspectives for the pre-operative diagnosis of soft tissue tumors in the molecular era. Pathol Res Pract. 2020 Jun;216(6):152923. Tomomi Yamaguchi, Toshiaki Akahane, Ohi Harada, et al. Next-generation sequencing in residual liquid-based cytology speciments for cancer genome analysis. Diagn Cytopathol. 2020 Jun 8. Allred DC, Harvey JM, Berardo M, Clark GM. 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Na-young Shin, Nyeong-Jin Kim, Jae-Joon Chung, Yong-Eun Chung,Jin-Yong Choi,Yong-Nyun Park. The Differential Imaging Features of Fat-Containing Tumors in the Peritoneal Cavity and Retroperitoneum: the Radiologic-Pathologic Correlation. Korean J Radiol. 2010; 11: 333-345. Cite Share Download PDF Status: Published Journal Publication published 04 Jan, 2022 Read the published version in Diagnostic Cytopathology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-900482","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":53909988,"identity":"c8299351-6bcb-4d59-a49b-977b910df81f","order_by":0,"name":"Kana Sugiyama","email":"","orcid":"","institution":"Department of Clinical Laboratory, Kanagawa Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Kana","middleName":"","lastName":"Sugiyama","suffix":""},{"id":53909989,"identity":"cdd42cab-9fd2-4bac-91a3-cb86a45c7534","order_by":1,"name":"Kota Washimi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYHACNoYEBgkDfh4GBmYQh3gtkj0kaQECA4MzYC1EAIPjx589eJhjYWx85vDDzwUMfHmEtZzJMTdI3CZhZna2zVh6BgNbMUEtZgdy2CSAWmzMzvOwMfMwsCU2ENRy/vkzsBbjfqK13EgwA2kxM+DtIVKL/Y03YC3GEmeOGUvzGBDhF8n+9GeSP7fVGfb3JD/8zFNxjHCIoQGDYwmkamGoIV3LKBgFo2AUDHsAAGRhNUNFqbIpAAAAAElFTkSuQmCC","orcid":"","institution":"Kanagawa cancer center","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Kota","middleName":"","lastName":"Washimi","suffix":""},{"id":53909990,"identity":"3305ea42-886c-4328-9628-64da47cb92e5","order_by":2,"name":"Shinya Sato","email":"","orcid":"","institution":"Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shinya","middleName":"","lastName":"Sato","suffix":""},{"id":53909991,"identity":"13696ea5-bc28-4c35-b65a-5ad5dc54dc76","order_by":3,"name":"Toru Hiruma","email":"","orcid":"","institution":"Department of Musculoskeletal Tumor Surgery, Kanagawa Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Toru","middleName":"","lastName":"Hiruma","suffix":""},{"id":53909992,"identity":"9acf9554-6841-43b1-a095-72654948a21b","order_by":4,"name":"Mai Sakai","email":"","orcid":"","institution":"Department of Clinical Laboratory, Kanagawa Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mai","middleName":"","lastName":"Sakai","suffix":""},{"id":53909993,"identity":"d77d3449-092b-4043-9863-a13777653910","order_by":5,"name":"Yoichiro Okubo","email":"","orcid":"","institution":"Department of Pathology, Kanagawa Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yoichiro","middleName":"","lastName":"Okubo","suffix":""},{"id":53909994,"identity":"36c0d372-33ed-4b59-b2b1-8a4e9099d410","order_by":6,"name":"Yohei Miyagi","email":"","orcid":"","institution":"Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yohei","middleName":"","lastName":"Miyagi","suffix":""},{"id":53909995,"identity":"9403e975-1e9e-41b2-a009-fc279acf746d","order_by":7,"name":"Tomoyuki Yokose","email":"","orcid":"","institution":"Department of Pathology, Kanagawa Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tomoyuki","middleName":"","lastName":"Yokose","suffix":""}],"badges":[],"createdAt":"2021-09-13 10:56:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-900482/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-900482/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1002/dc.24928","type":"published","date":"2022-01-04T07:16:32+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":14018874,"identity":"540b6202-faf2-49f3-8891-6622dbd8063e","added_by":"auto","created_at":"2021-09-27 14:43:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2143369,"visible":true,"origin":"","legend":"Cytological findings from Papanicolaou-stained tissue sample. a: The absence of nuclear pleomorphism at low magnification. b: Prominent nuclear pleomorphism observed at low magnification. c: Cells with intranuclear vacuoles observed at high magnification. d: Multinucleated cells observed at high magnification. e: Cells with nuclear enlargement and unequal nuclear size observed at low magnification. f: Cells with nuclear enlargement and prominent nucleoli observed at high magnification. g: A cell with hyperchromatosis observed at high magnification. h–l: Large atypical cells defined as cells with increased chromatin and enlarged irregular nucleus observed at high magnification. (Scale size: 50 µm)","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/64cdfcc122415df6fef40c1d.png"},{"id":14018875,"identity":"a17e03f9-62b5-4025-83b2-81592a157590","added_by":"auto","created_at":"2021-09-27 14:43:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":3404020,"visible":true,"origin":"","legend":"Fluorescence in situ hybridization (FISH) for MDM2. MDM2 is seen as an orange signal; CEP12, as a green signal. a: Formalin-fixed paraffin-embedded (FFPE) specimen of case 1. High level of MDM2 signal amplification. b: Papanicolaou-stained specimen of case 1. High level of MDM2 signal amplification. c: FFPE specimen of case 2. Moderate amplification of MDM2 signal amplification. d: Papanicolaou-stained specimen of case 2. Moderate amplification of MDM2 signal amplification.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/c7a7a8c1e58b3bfcfc8669df.png"},{"id":14018876,"identity":"b97f5341-e198-4ddc-a042-2516145ed691","added_by":"auto","created_at":"2021-09-27 14:43:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2292388,"visible":true,"origin":"","legend":"Fluorescence in situ hybridization (FISH) for MDM2 using a Papanicolaou-stained specimen obtained from a case that did not show MDM2 amplification. The strong background staining made it difficult to evaluate the signal.","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/65cb0d182b2fae1c848bbf8b.png"},{"id":14019298,"identity":"7f1d52c6-4ac4-4c57-a61e-b7fdcd157002","added_by":"auto","created_at":"2021-09-27 14:46:35","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3147051,"visible":true,"origin":"","legend":"Comparison of histological images of the most conspicuous large atypical cells in all Hematoxylin Eosin stained glass slides obtained from formalin-fixed paraffin-embedded specimens and the most conspicuous large atypical cells in the review of an area of about 1 cm2 in the Papanicolaou-stained specimens prepared from small pieces of 2–3 mm. All figures are at the same high magnification. a: Papanicolaou staining in case 9. b: HE staining in case 9. c: Papanicolaou staining in case 12. d: HE staining in case 12. Fig. 5. Fluorescence in situ hybridization using cytological specimens is possible with high accuracy and could be a potential strategy for diagnosing adipocytic tumors using cytological specimens. ","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/605cd4959d03a63159083aa1.png"},{"id":14018878,"identity":"966c0483-67b4-4856-aee6-463ddd14cce9","added_by":"auto","created_at":"2021-09-27 14:43:35","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":135152,"visible":true,"origin":"","legend":"Fluorescence in situ hybridization (FISH) using cytological specimens is possible with high accuracy and could be a potential strategy for diagnosing adipocytic tumors using cytological specimens. ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas.","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/57dcbf359e31a5c6c766556c.png"},{"id":17003601,"identity":"9cbdb1fb-ee29-49ce-b083-4052945ede50","added_by":"auto","created_at":"2022-01-05 07:16:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8187987,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-900482/v1/a9879b2e-72cb-4b75-80a5-aa6e37d096bf.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eDifferential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAdipocytic tumors are the most common soft tissue tumors and mostly comprise lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL). ALT/WDL can become highly malignant by dedifferentiation or recurrence, thereby making it important to differentiate them from lipomas, which are benign tumors, for appropriate treatment and for determining the follow-up period after tumor resection.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e The mouse double minute 2 homolog (MDM2) protein suppressively regulates \u003cem\u003eTP53\u003c/em\u003e, a tumor suppressor gene. Fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization (FISH) analysis of formalin-fixed paraffin-embedded (FFPE) tissues has revealed \u003cem\u003eMDM2\u003c/em\u003e amplification in ALT/WDL and is currently used to differentiate these tumors.\u003csup\u003e\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e With the development of new molecular tests showing high diagnostic specificity, fine-needle aspiration cytology (FNAC) has begun to gain acceptance for preoperative assessment of soft tissue tumors.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e FNAC represents a versatile, low-cost, well-tolerated diagnostic strategy with obvious advantages over histological biopsies.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, a detailed comparison of the cytological findings of lipoma and ALT/WDL with \u003cem\u003eMDM2\u003c/em\u003e amplification has not yet been reported. In this study, we compared the cytological features of lipoma and ALT/WDL and used the cytological findings for their differential diagnosis. We also performed FISH to examine \u003cem\u003eMDM2\u003c/em\u003e amplification in cytological specimens and to evaluate the usefulness of cytology for differential diagnosis of adipocytic tumors.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003eWe reviewed the clinical and histological data of 20 patients with lipoma and ALT/WDL who had undergone resection at Kanagawa Cancer Center between 2018 and 2020. One ALT/WDL case showed partially dedifferentiated areas. We evaluated age, sex, and maximum tumor diameter as the clinical parameters. As cytological specimens, tissue samples (2\u0026ndash;3 mm in size) were randomly collected from the center of the surgical specimens, mimicking FNAC, and subjected to Papanicolaou staining. If the case showed a dedifferentiated area, the sample was collected from the ALT/WDL area. Six cytotechnologists (CTs) evaluated the cell morphology, number of lipoblasts, size of adipocytes, nuclear pleomorphism, intranuclear vacuoles, multinucleated cells, nuclear enlargement, unequal size of nuclei, irregular nuclear borders, hyperchromatosis, prominent nucleoli, large atypical cells, and background necrosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea\u0026ndash;g). Large atypical cells were defined as cells with increased chromatin and irregular nuclear enlargement (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eh\u0026ndash;l). The morphology of each cell was evaluated on a score of 4 (1: almost none, 2: a little, 3: common, 4: prominent), and background necrosis was assessed on a score of 2 (0: absent, 1: present). Furthermore, each CT estimated the histological type of the lipoma or ALT/WDL based on the cytological findings. More than 200 cells were examined using a WinROOF2018 image analyzer (MITANI Corporation, Tokyo, Japan), and the short nuclear diameter was measured for samples subjected to Papanicolaou staining.\u003c/p\u003e \u003cp\u003eThe FFPE blocks of the surgical samples were prepared for histological examination. Resected specimens were fixed in 10% neutral-buffered formalin. At least one block per centimeter of the largest diameter of the tumor was prepared for histological evaluation. If the maximum diameter was 10 cm, more than 10 FFPE blocks were prepared for histological evaluation. The two pathologists evaluated nuclear atypia of adipocytes and atypical stromal cells and made a histological diagnosis. Immunostaining for MDM2 and CDK4 and FISH examination for \u003cem\u003eMDM2\u003c/em\u003e were performed in all cases using FFPE specimens. In addition, in four cases, FISH for \u003cem\u003eMDM2\u003c/em\u003e was performed using Papanicolaou-stained specimens.\u003c/p\u003e \u003cp\u003eThe histological type determined by at least four of six CTs was used as the cytological diagnosis result for analysis. We used the Mann\u0026ndash;Whitney U test to analyze the association between the clinical findings, histological diagnosis, cytological diagnosis, and the length of the short diameter of the cell nuclei and the presence of \u003cem\u003eMDM2\u003c/em\u003e amplification. We analyzed the association between each cytological finding and each diagnosis based on Papanicolaou-stained specimens using Spearman\u0026rsquo;s correlation and then examined the mean values. We also analyzed the association between the total score of the cytological findings of the six CTs and the presence of \u003cem\u003eMDM2\u003c/em\u003e amplification using Spearman\u0026rsquo;s correlation. Statistical analysis was performed using SPSS version 26 software (SPSS Inc., Chicago, IL, USA). Results with \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eImmunohistochemistry\u003c/h2\u003e \u003cp\u003eDeparaffinized tumor sections were stained for CDK4 (Clone DCS-31, Thermo Fisher Scientific, Waltham, MA, USA) and MDM2 (Clone IF2, Thermo Fisher Scientific) using the heat-induced epitope retrieval method. Appropriate positive and negative controls were used in all analyses. Immunostaining was evaluated based on the intensity and proportion of tumor cell staining in each specimen. The intensity of staining was defined by applying Allred scoring\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e as follows: 3+, strong; 2+, moderate; 1+, weak; \u0026minus;, no staining. The proportion of staining was measured for each specimen and classified by applying Allred scoring as follows: 5, \u0026gt;\u0026thinsp;66%; 4, 66\u0026ndash;33%; 3, 33\u0026ndash;10%; 2, 10\u0026ndash;1%; 1, \u0026lt;\u0026thinsp;1%; 0, 0%. Cases were defined as MDM2-positive if the Allred score of the marker (defined as the combined value of the intensity score and proportion score) was more than 1. Moreover, cases were considered as CDK4-positive if the Allred score of the marker was more than 5.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eFISH analysis\u003c/h2\u003e \u003cp\u003eFISH for \u003cem\u003eMDM2\u003c/em\u003e was performed in all 20 cases using FFPE tissues with the Vysis\u0026reg;ฎ LSI\u0026reg;ฎ MDM2 SpectrumOrange Probe (CEP\u0026reg;ฎ 12 [D12Z3], Abbott Molecular, Des Plaines, IL, USA) according to the manufacturer\u0026rsquo;s protocol. The probe cocktail decorates the human chromosomal region harboring \u003cem\u003eMDM2\u003c/em\u003e with an orange signal and the centromeric region of chromosome 12 with a green signal. The signals were scored by counting a minimum of 20 non-overlapping nuclei per case, and the average of \u003cem\u003eMDM2\u003c/em\u003e and centromere 12 signals was calculated. An \u003cem\u003eMDM2\u003c/em\u003e/chromosome 12 signal ratio of \u0026gt;\u0026thinsp;2.0 was considered to represent \u003cem\u003eMDM2\u003c/em\u003e amplification (amplification-positive).\u003c/p\u003e \u003cp\u003eFISH for \u003cem\u003eMDM2\u003c/em\u003e was performed using the Papanicolaou-stained specimen to evaluate the cytological findings in four cases. Using FISH in FFPE samples, two cases showed \u003cem\u003eMDM2\u003c/em\u003e amplification whereas two cases did not. After xylene was removed using 100% ethanol, the samples were destained with ethanol hydrochloride for 2\u0026ndash;3 h. Next, the samples were washed with 100% ethanol and incubated overnight at room temperature (20\u0026ndash;30\u0026deg;C). The specimens were immersed in 0.2% hydrochloride for 20 min, followed by immersion in distilled water for 1 min, a wash buffer for 5 min, and finally protease solution (Abbott Molecular; pre-warmed to 37\u0026deg;C\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg;C) for 10 min. Samples were again immersed in wash buffer for 5 min, and the procedure was repeated. Next, the samples were immersed in 10% neutral-buffered formalin for 10 min followed by immersion in wash buffer for 5 min, and the procedure was repeated. Finally, the Vysis\u0026reg;ฎ LSI\u0026reg;ฎ MDM2 SpectrumOrange Probe was added to the denatured DNA, and hybridization was carried out at 73\u0026deg;C for 3 min, followed by overnight incubation at 37\u0026deg;C. The cells were washed to eliminate non-specific signals by immersing them in hybridization wash buffer (2X SSC/0.3% NP-40; Abbott Molecular) preheated to 72\u0026deg;C\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u0026deg;C for 2 min. The specimens were immersed in wash buffer and DAPI was added, followed by observation with fluorescence microscope Ti-E equipped with a Triple Bandpass Filter Set, DAPI/Green/Orange v2 (Nikon Corporation, Tokyo, Japan).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe participants included 13 men and 7 women, with a mean age of 56 years. The most commonly affected site was the thigh (n\u0026thinsp;=\u0026thinsp;10), and the mean maximum tumor diameter was 133 mm. Seven cases were histologically diagnosed as lipoma and 13 cases as ALT/WDL. The mean nucleus short diameter of tumor cells measured from the Papanicolaou-stained samples was 4.02 \u0026micro;m, with a median of 3.75 \u0026micro;m. The short diameter of the nucleus in most tumor cells observed in Papanicolaou-stained samples was less than 5 \u0026micro;m, and a few tumor cells had nuclei with a short diameter of more than 10 \u0026micro;m. Immunostaining evaluation using FFPE tissues revealed 9 MDM2-positive cases and 11 CDK4-positive cases. In 12 cases, \u003cem\u003eMDM2\u003c/em\u003e amplification was observed by performing FISH on FFPE tissues (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathological findings of patients with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(min, max)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale/Female, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e13/7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years \u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e56\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(19, 90)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size, mm \u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e133\u0026thinsp;\u0026plusmn;\u0026thinsp;73\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(50, 350)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLocation, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eThigh\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNeck\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eHead\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eButtocks\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFoot\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInguinal region\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eLower leg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eUpper arm\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eRetroperitoneum\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eLipoma\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eALT/WDL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNucleus short diameter, \u0026micro;m \u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(3.26, 5.03)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e(Papanicolaou staining)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMaximum diameter\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e10.07\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(6.21, 14.82)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProportion of nucleus diameter, % \u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;5 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e20.4\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(3.4, 38.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e(Papanicolaou staining)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;6 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0.5, 24.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;7 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0, 18.3)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;8 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0, 9.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;9 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0, 4.2)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e\u0026ge;\u0026thinsp;10 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0, 2.9)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eMDM2\u003c/span\u003e \u003cb\u003eFISH (20 cells) \u0026Dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMDM2 signals total\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e168.5 (33\u0026ndash;230)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(28, 449)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMDM2/CEP\u0026reg;12 ratio\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.95 (0.98\u0026ndash;6.70)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e(0.8, 13.6)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAmplification +/\u0026minus;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e12/8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u0026dagger;values are the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (min, max). \u0026Dagger;values are the median (interquartile range). ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; FISH, fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn nine cases, at least four out of six CTs predicted ALT/WDL based on the cytological characteristics of the Papanicolaou-stained tissue samples. Moreover, \u003cem\u003eMDM2\u003c/em\u003e amplification was observed by FISH in each of these nine cases. The nucleus short diameter was significantly longer (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with a larger standard deviation in cases with \u003cem\u003eMDM2\u003c/em\u003e amplification, indicating greater variation in the nuclear size. Cells in which the short diameter of the nucleus was greater than 9 \u0026micro;m were not observed in cases in which \u003cem\u003eMDM2\u003c/em\u003e was not amplified (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between clinical findings, immunostaining results, and the length of the short diameter of cell nuclei in cases with and without \u003cem\u003eMDM2\u003c/em\u003e amplification detected by FISH.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eMDM2\u003c/em\u003e amplification (+)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eMDM2\u003c/em\u003e amplification (\u0026minus;)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e12 cases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e8 cases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMDM2 signal (20 cells) \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e247.7\u0026thinsp;\u0026plusmn;\u0026thinsp;89.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCEP signal (20 cells) \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e36.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e33.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMDM2 / CEP12 ratio \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e7.24\u0026thinsp;\u0026plusmn;\u0026thinsp;3.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePercentage of cells with MDM2 / CEP12 ratio\u0026thinsp;\u0026gt;\u0026thinsp;2.0 \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e80.8\u0026thinsp;\u0026plusmn;\u0026thinsp;10.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMale/Female, n\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e8 / 4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e5 / 3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.910\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge, years \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e58\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e51\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.427\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTumor size, mm \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e156\u0026thinsp;\u0026plusmn;\u0026thinsp;80\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e97\u0026thinsp;\u0026plusmn;\u0026thinsp;44\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.082\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eHistologic specimen\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological diagnosis ALT/WDL, cases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImmunohistochemistry\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMDM2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003epositive cases \u0026dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eCDK4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eCytologic specimen\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCytological diagnosis ALT/WDL, cases \u0026Dagger;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNucleus short diameter, \u0026micro;m \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAverage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eSD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMaximum diameter\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e11.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e7.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProportion of nucleus diameter, % \u0026sect;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;5 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e26.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;6 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e14.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;7 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;8 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;9 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e≧\u0026thinsp;10 \u0026micro;m\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026dagger;allred score MDM2: more than 1, CDK4: more than 5. \u0026Dagger;cases that more than half of the cytotechnologists judged as ALT/WDL. \u0026sect;values are the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. ALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; FISH, fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe six CTs identified the samples as lipoma or ALT/WDL based on the cytological findings with a concordance rate of 88.3%. The mean concordance rate of identifying samples as lipoma or ALT/WDL based on cytological and histopathological findings was 76.7% (65% minimum, 90% maximum), whereas that based on cytological findings and \u003cem\u003eMDM2\u003c/em\u003e amplification by FISH was 78.3% (70% minimum, 85% maximum). Cytological findings with a relatively high concordance rate among evaluation by CTs included lipoblasts, necrosis, large atypical cells, multinucleated cells, and pleomorphism. The cytological findings that correlated significantly with \u003cem\u003eMDM2\u003c/em\u003e amplification by FISH included pleomorphism, unequal size of adipocytes, irregular nuclear borders, hyperchromatosis, unequal size of nuclei, nuclear enlargement, prominent nucleoli, large atypical cells, and multinucleated cells. The relationship between cytological findings and ALT/WDL identification by each CT was relatively strong for pleomorphism, nuclear enlargement, and unequal nuclear size (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In the group with \u003cem\u003eMDM2\u003c/em\u003e amplification, the total scores of large atypical cells, multinucleated cells, and pleomorphism were higher. The mean total score of the above three findings was less than 5 in the group without \u003cem\u003eMDM2\u003c/em\u003e amplification, although some cases had total scores of less than 5 in the group with \u003cem\u003eMDM2\u003c/em\u003e amplification. A single CT rescreened a 1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. Sixty-seven percent (8/12 cases) of the cases with \u003cem\u003eMDM2\u003c/em\u003e amplification had large atypical cells. No large atypical cells were found in lipoma cases (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean concordance rate between cytological findings among cytotechnologists (CTs).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eEvaluation concordance rate, % \u0026dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCytological diagnosis \u0026dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eMDM2/CEP12 ratio\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003er.\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003cb\u003e-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003er.\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003cb\u003e-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLipoblasts\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e94.9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.204\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.432\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.312\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.181\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNecrosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e90.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.400\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.163\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.416\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.068\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLarge atypical cells\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e73.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.680\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.022\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.601\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultinucleated cells\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e66.7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.641\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.035\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.559\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePleomorphism\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e65.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.812\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.781\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnequal size of adipocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e60.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.619\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.056\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.711\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIrregular nuclear borders\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e60.0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.712\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.051\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.694\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProminent nucleoli\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e57.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.593\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.608\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnequal size of nuclear\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e56.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.764\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.668\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNuclear enlargement\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e55.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.780\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.640\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHyperchromatosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e54.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.688\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.170\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.693\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIntranuclear vacuoles\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e52.4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.152\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.381\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e-0.116\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.625\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCytological diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e88.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.693\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eMeans determined by the six CTs were used for evaluating the association between cytological findings and each individual\u0026rsquo;s estimated histological type by Papanicolaou-stained specimens. The association between the total score of cytological findings of six CTs and the presence of \u003cem\u003eMDM2\u003c/em\u003e amplification is shown. \u0026dagger;Values are the means\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of \u003cem\u003eMDM2\u003c/em\u003e amplification by FISH using FFPE specimens and histological diagnosis and cytological impression.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFISH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistological diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCytological impression \u0026dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eCytological morphology Score Average (1\u0026ndash;4) \u0026Dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLarge atypical cell re-examination \u0026sect;\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of MDM2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMDM2/CEP12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLarge atypical cells\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMultinucleated cells\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePleomorphism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e192\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLipoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e283\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e449\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLiposarcoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003eThe mean value of the cytological morphology scores of six CTs. A single CT rescreened a 1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. \u0026dagger;More than four out of the six CTs\u0026rsquo; results. \u0026Dagger;Average of the scores evaluated by six CTs. \u0026sect;A single CT rescreened a 1 cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. FISH, fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization; FFPE, formalin-fixed paraffin-embedded specimens.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFISH examination was performed on Papanicolaou-stained specimens from two cases in which \u003cem\u003eMDM2\u003c/em\u003e amplification was confirmed by FISH using FFPE specimens (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Case 1 exhibited relatively high \u003cem\u003eMDM2\u003c/em\u003e signals in FFPE specimens, as well as higher signals in Papanicolaou-stained specimens, whereas case 2 exhibited relatively low \u003cem\u003eMDM2\u003c/em\u003e signals in FFPE specimens and lower signals in Papanicolaou-stained specimens. Signal evaluation by performing FISH on Papanicolaou-stained FFPE specimens from two cases without \u003cem\u003eMDM2\u003c/em\u003e amplification was difficult because of the presence of strong background signals (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of FISH using FFPE and Papanicolaou-stained specimens.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMDM2 \u0026dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCEP12 \u0026dagger;\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMDM2 / CEP12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMDM2/CEP12\u0026thinsp;\u0026gt;\u0026thinsp;2.0 cells (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eCase 1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFFPE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e449\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e33\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e13.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e95\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePapanicolaou\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e357\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e41\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e8.3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e100\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eCase 2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFFPE\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e156\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e61\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2.6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e65\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003ePapanicolaou\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e201\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e64\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e3.1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e70\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u0026dagger;Number of signals in 20 cells. FISH, Fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization; FFPE, formalin-fixed paraffin-embedded specimens.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe evaluated and compared cytological findings, \u003cem\u003eMDM2\u003c/em\u003e amplification, and histological diagnosis to identify patient samples either as lipoma or ALT/WDL. The concordance rate for distinguishing between these two conditions based on cytologic specimens and histological findings was 76.7%, indicating that small cytological specimens can predict the whole tissue histological findings with high probability. CTs focused on pleomorphism, nuclear enlargement, and unequal size of nucleus in predicting lipoma or ALT/WDL, but the concordance rates between CTs were low for parameters such as nuclear enlargement and nuclear size. The cytological findings with a high concordance rate among CTs were strongly associated with histology and \u003cem\u003eMDM2\u003c/em\u003e amplification, multinucleated cells, pleomorphism, and large atypical cells. If the sum of the scores for the multinucleated cells, pleomorphism, and large atypical cells was 3 for lipoma and 4\u0026ndash;12 for ALT/WDL, and the \u003cem\u003eMDM2\u003c/em\u003e amplification indicated ALT/WDL, positive sensitivity was 90.3%, negative sensitivity was 64.6%, and the total concordance rate was 80.0%. Specimens from ALT/WDL cases, showing \u003cem\u003eMDM2\u003c/em\u003e amplification and all three findings with score 1, showed some multinucleated cells; detailed evaluation of these findings may increase the positive sensitivity. However, few multinucleated cells were observed in lipoma cases without \u003cem\u003eMDM2\u003c/em\u003e amplification. A single CT rescreened a 1-cm\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e area of the Papanicolaou-stained specimen in each case and counted the number of large atypical cells. As large atypical cells were not found in the lipoma cases, it was considered a highly specific cellular finding of ALT/WDL. However, the sensitivity of large atypical cells was not high. Comprehensive evaluation of multinucleated cells and pleomorphism is important for predicting the diagnosis of ALT/WDL. \u003cem\u003eMDM2\u003c/em\u003e amplification may be predicted using cytological specimens with even greater probability by considering the above-mentioned three cytological findings, namely multinucleated cells, pleomorphism, and large atypical cells.\u003c/p\u003e \u003cp\u003eIn one case, the histological findings indicated ALT/WDL, and amplification of \u003cem\u003eMDM2\u003c/em\u003e was not observed by FISH. This case was diagnosed as ALT/WDL because of the presence of a small number of large nucleated cells. If it is difficult to identify a distinct atypical cell, \u003cem\u003eMDM2\u003c/em\u003e amplification by FISH must be confirmed for final diagnosis. In this case, four of six CTs presumed the sample to be a lipoma based on the cytological specimens. In a few cases of ALT/WDL, atypical cells were identified relatively easily in cytological specimens, even when it was difficult to identify atypical cells in the histological specimens (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Although tissue specimens can be examined over a wide area, cytological specimens can be used to evaluate nuclear atypia in more detail and may help improve diagnostic accuracy in combination with tissue specimens.\u003c/p\u003e \u003cp\u003eThe length of the nucleus short diameter in the Papanicolaou-stained cytological specimens was significantly greater in cases showing \u003cem\u003eMDM2\u003c/em\u003e amplification. Additionally, a significant difference in SD values was also observed, suggesting that unequal nuclear size was prominent in the \u003cem\u003eMDM2\u003c/em\u003e amplification group, which may reflect as pleomorphism in cytological findings. In cases without \u003cem\u003eMDM2\u003c/em\u003e amplification, few cells with a nucleus short diameter greater than 7 \u0026micro;m were observed, but none of the cells had a nucleus short diameter greater than 9 \u0026micro;m.\u003c/p\u003e \u003cp\u003eAlthough most adipocytic tumors are lipoma and ALT/WDL, other adipocytic neoplasms should be included when performing differential diagnosis before surgery. These include adipocytic tumors, such as angiolipomas, myolipomas, chondrolipomas, spindle cell lipomas, pleomorphic lipomas, atypical spindle cell/pleomorphic lipomatous tumors, lipomatous myxoid liposarcomas, dedifferentiated liposarcomas, and pleomorphic liposarcomas. These tumors were not considered in the present study. Angiolipomas are generally more common among young individuals in their late teens and early 20s.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Myolipoma is a rare tumor that does not show atypical cells, as observed in ALT/WDL.\u003csup\u003e8\u003c/sup\u003e A chondroid lipoma is a rare tumor composed of relatively cohesive clusters of mature adipocytes and variably sized lipoblasts in a chondromyxoid matrix.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Approximately 80% of spindle cell lipomas and pleomorphic lipomas arise within the subcutaneous tissue of the posterior neck, back, and shoulders.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Atypical spindle cell/pleomorphic liposomal tumors in the hands and feet include mild to moderately atypical spindle cells, adipocytes, lipoblasts, and pleomorphic cells.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e These benign adipocytic neoplasms can be differentiated from ALT/WDL by examining \u003cem\u003eMDM2\u003c/em\u003e amplification. Preoperative diagnosis of myxoid liposarcoma is important because preoperative radiotherapy and excision methods differ from those for ALT/WDL. Myxoid liposarcoma is more common among individuals in their 30s and 40s and tends to be less pleomorphic than ALT/WDL. Identifying \u003cem\u003eDDIT3\u003c/em\u003e rearrangement using FISH break-apart probes is a sensitive, specific strategy for the diagnosis of myxoid liposarcoma.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Dedifferentiated liposarcoma often indicates ATL/WDL around the tumor, as revealed by imaging findings.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Preoperative imaging findings rarely indicate pleomorphic liposarcoma as an adipocytic tumor.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCurrently, while considering treatment strategies for adipocytic tumor, it is important to differentiate among benign lipoma, ALT/WDL with the potential for recurrence and malignancy, and myxoid liposarcoma with the potential for distant metastasis that requires wide resection. FISH examination plays an important role in differentiating among these three conditions. In the present study, the results of \u003cem\u003eMDM2\u003c/em\u003e amplification obtained by FISH of cytological specimens were consistent with the FISH results obtained using FFPE specimens. In two cases with no \u003cem\u003eMDM2\u003c/em\u003e amplification, it was difficult to detect signals by FISH using Papanicolaou-stained specimens. This may be attributed to the strong background staining. In order to avoid background signals, it is necessary to consider methods such as dividing the sample for analysis and conducting Papanicolaou staining and FISH separately. It is necessary to optimize the assay conditions to improve the accuracy of \u003cem\u003eMDM2\u003c/em\u003e FISH in the cytological specimens of adipocytic tumors. If FISH for \u003cem\u003eDDIT3\u003c/em\u003e can be performed on cytological specimens, several adipocytic tumors may be predicted from these samples (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is possible to detect genes using small specimens, and minimally invasive FNAC may be used for preoperative diagnosis of various tumors, including soft tissue tumors.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e In the era of genetic analysis of small tissue specimens, preoperative diagnosis by FNAC, a minimally invasive test, may play a major role in determining treatment plans. Familiarity with the cell morphology of cytological specimens derived from tumors is important for making a differential diagnosis. Preoperative diagnosis of lipoma or ALT/WDL can provide important information for deciding the treatment plan. In the future, it will be important to examine and analyze the diagnostic accuracy of cytological morphology in actual aspiration biopsy specimens. Given that the size of the patient dataset was small (n\u0026thinsp;=\u0026thinsp;20), we will consider a follow-up study with a larger cohort. Our results may facilitate differential diagnoses for patients with lipoma and ALT/WDL and assist clinicians in making treatment decisions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eLipoma or ALT/WDL can be predicted with a high probability by evaluating the cytological findings of multinucleated cells, pleomorphism, and large atypical cells in Papanicolaou-stained tissue specimens. However, it is sometimes difficult to confirm the diagnosis based only on cell morphology, and further confirmation of \u003cem\u003eMDM2\u003c/em\u003e amplification by FISH is important. If the accuracy of \u003cem\u003eMDM2\u003c/em\u003e FISH in cytological specimens can be improved, cytology may become a useful tool for the preoperative differential diagnosis of adipocytic tumors.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALT/WDL, atypical lipomatous tumor/well-differentiated liposarcomas; CTs, cytotechnologists; FFPE, formalin-fixed paraffin-embedded specimens; FISH, fluorescence \u003cem\u003ein situ\u003c/em\u003e hybridization; FNAC, fine-needle aspiration cytology.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe applied the opt-out method to obtain patient consent for this study. This study was approved by the research ethics review committee of Kanagawa Cancer Center (approval no. 2020 epidemiology-22).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eAll data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis research\u0026nbsp;was\u0026nbsp;supported by joint research funding from Kanagawa Cancer Center Hospital-Research Institute Joint Study (grant no. 2020-12) and a grant-in-aid for scientific research (grant no. JP 20K16210) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKS: Evaluation of cell morphology and FISH results, immunostaining. KW: Substantial contributions to the conception and design of the work, analysis of results, histological diagnosis, and writing of the manuscript.\u0026nbsp;SS: Analysis of clinicopathological findings.\u0026nbsp;TH:\u0026nbsp;Analysis of clinicopathological findings.\u0026nbsp;MS: Evaluation of cell morphology. KK: Evaluation of cell morphology. YO:\u0026nbsp;Analysis of clinicopathological findings. YM:\u0026nbsp;Analysis of clinicopathological findings. TY:\u0026nbsp;Analysis of clinicopathological findings, histological diagnosis. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to Dr. Masayuki Takagi for advice on the histological diagnosis and to the technical staff at Kanagawa Cancer Center, Mei Sawaguchi, Ryuji Nasu, Shigeko Iwanade, Tomomi Hasumoto, and Kazuhisa Kitamura, for evaluating cytological findings and their expert technical assistance.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSatoshi Nagano, Masahiro Yokouchi, Takao Setoguchi, et al. Differentiation of lipoma and atypical lipomatous tumor by a scoring system: implication of increased vascularity on pathogenesis of liposarcoma. BMC Muxculoskelet Disord. 2015; 16: 36.\u003c/li\u003e\n \u003cli\u003eSirvent N, Coindre JM, Maire G, et al. Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR. Am J Surg Pathol. 2007 Oct;31(10)\u0026nbsp;:1476-1489.\u003c/li\u003e\n \u003cli\u003eCreytens D, Van Gorp J, Speel EJ, Ferdinande F. Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis. Anticancer Res. 2015 Nov;84(11):2222-2230.\u003c/li\u003e\n \u003cli\u003eTap WD, Eilber FC, Ginther C, et al. Evaluation of well-differentiated/de-differentiated liposarcoma by high-resolution oligonucleotide array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2011 Feb;50(2):95-112.\u003c/li\u003e\n \u003cli\u003eFrancesca Pagliuca, Andrea Ronchi, Immacolata Cozzolino, Marco Montella,Federica Zito Marino,Renato Franco. Mesenchymal neoplasms: Is it time for cytology? New perspectives for the pre-operative diagnosis of soft tissue tumors in the molecular era. Pathol Res Pract. 2020 Jun;216(6):152923.\u003c/li\u003e\n \u003cli\u003eTomomi Yamaguchi, Toshiaki Akahane, Ohi Harada, et al. Next-generation sequencing in residual liquid-based cytology speciments for cancer genome analysis. Diagn Cytopathol. 2020 Jun 8.\u003c/li\u003e\n \u003cli\u003eAllred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155-168.\u003c/li\u003e\n \u003cli\u003eWHO Classification of Tumours Editorial Board（ed.）：WHO Classification of Tumours：Soft Tisuue＆Bone Tumors, 5th ed, IARC Press, Lyon, 2020. 23-26, 34-44.\u003c/li\u003e\n \u003cli\u003eGisselsson D, Domanski HA, Hoglund M, et al. Unique cytological features and chromosome aberrations in chondroid lipoma: a case report based on fine-needle aspiration cytology, histopathology, electron microscopy, chromosome banding, and molecular cytogenetics. Am J Surg Pathol. 1999 Oct;23(10):1300-1304\u003c/li\u003e\n \u003cli\u003eYang YJ, Damron TA, Ambrose JL. Diagnosis of chondroid lipoma by fine-needle aspiration biopsy. Arch Pathol Lab Med. 2001 Sep;125(9)1224-1226.\u003c/li\u003e\n \u003cli\u003eEnzinger FM, Harvey DA, Spindle cell lipoma. Cancer. 1975 Nov;36(5):1852-1859.\u003c/li\u003e\n \u003cli\u003eShmookler BM, Enzinger FM. Pleomorphic lipoma: a benign tumor simulating liposarcoma. A clinicopathologic analysis of 48 cases. Cancer. 1981 Jan 1;47(1):126-133.\u003c/li\u003e\n \u003cli\u003eNa-young Shin, Nyeong-Jin Kim, Jae-Joon Chung, Yong-Eun Chung,Jin-Yong Choi,Yong-Nyun Park. The Differential Imaging Features of Fat-Containing Tumors in the Peritoneal Cavity and Retroperitoneum: the Radiologic-Pathologic Correlation. Korean J Radiol. 2010; 11: 333-345.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Cytology, Lipoma, Well-differentiated liposarcoma, Fluorescence in situ hybridization, MDM2","lastPublishedDoi":"10.21203/rs.3.rs-900482/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-900482/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAdipocytic tumors are the most common soft tissue tumors, with lipomas and atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDL) comprising the majority of cases. Preoperative differential diagnosis of lipoma or ALT/WDL can provide important information for decisions regarding treatment. We evaluated the cytological findings of 20 cases of lipoma and ALT/WDL.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Fluorescence \u003cem\u003ein situ \u003c/em\u003ehybridization (FISH) was performed on formalin-fixed paraffin-embedded specimens (FFPE) to examine mouse double minute 2 homolog (\u003cem\u003eMDM2\u003c/em\u003e) amplification in all cases. Tissue samples were collected from the center of the surgical materials, stained with Papanicolaou, and evaluated for 12 cytological parameters by six cytotechnologists.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe findings regarding large atypical cells, multinucleated cells, and nuclear pleomorphism were highly concordant among the cytotechnologists and were associated with \u003cem\u003eMDM\u003c/em\u003e2 amplification. Large atypical cells, considered a highly specific feature of ALT/WDL, were not observed in the lipoma cases. However, the sensitivity of the large atypical cell findings was not high (67%), and therefore, comprehensive evaluation of multinucleated cells and pleomorphism is crucial for predicting the diagnosis of ALT/WDL. FISH of \u003cem\u003eMDM2\u003c/em\u003e on Papanicolaou-stained specimens was performed in four cases. In two cases, the results were similar to those of \u003cem\u003eMDM2\u003c/em\u003e FISH performed on FFPE sections and were reproducible, whereas in two other cases, the signal could not be evaluated because of the strong background coloration. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Cytology specimens may be useful for preoperative diagnosis of adipocytic tumors, particularly if the FISH conditions for Papanicolaou-stained specimens and the detection accuracy of \u003cem\u003eMDM2\u003c/em\u003e amplification can be improved.\u003c/p\u003e","manuscriptTitle":"Differential Diagnosis of Lipoma and Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma by Cytological Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-09-27 14:43:33","doi":"10.21203/rs.3.rs-900482/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"13222112-8c3a-42a5-ac15-dcd093055350","owner":[],"postedDate":"September 27th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":7460837,"name":"Pathology"}],"tags":[],"updatedAt":"2025-10-15T01:57:33+00:00","versionOfRecord":{"articleIdentity":"rs-900482","link":"https://doi.org/10.1002/dc.24928","journal":{"identity":"diagnostic-cytopathology","isVorOnly":true,"title":"Diagnostic Cytopathology"},"publishedOn":"2022-01-04 07:16:32","publishedOnDateReadable":"January 4th, 2022"},"versionCreatedAt":"2021-09-27 14:43:33","video":"","vorDoi":"10.1002/dc.24928","vorDoiUrl":"https://doi.org/10.1002/dc.24928","workflowStages":[]},"version":"v1","identity":"rs-900482","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-900482","identity":"rs-900482","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}