Liposarcoma Research Articles

Leiomyosarcoma and liposarcoma in young patients: The national netsarc+ network experience

BackgroundLeiomyosarcoma (LMS) and liposarcoma (LPS) are ultra-rare sarcomas in pediatric (0–18 years) and young adult (19−30) populations. We aimed to analyze their clinical characteristics at these young ages and to determine whether they should be considered with the same therapeutic strategy in both populations. MethodsNational retrospective multicenter study of all young patients (0–30 years) included in the sarcoma database “ConticaBase”, treated for LMS or LPS between 2010 and 2019 via the national NETSARC+ network, with available pathology/biology review. FindingsA total of 218 patients were identified, 34 children (nine LMS, 25 LPS) and 184 young adults (58 LMS, 126 LPS). Myxoid/Round Cell LPS (M/RC-LPS) was the most frequent LPS subtype (72 %). All children had localized LMS and LPS, versus 52/58 and 116/126 respectively in adults. Clinical presentation of LMS and all LPS subtypes was comparable in both populations, except for a preferential limb location of LMS in children. The therapeutic strategy was mainly based on primary surgery in LMS (9/9 children, 52/58 adults) and for LPS (respectively 25/25 and 122/126), exclusively or with adjuvant radiotherapy and systemic treatment. With a median follow-up of 62.4 months (range, 2.5–146), 5-year overall survival was respectively 83 % [95 % CI, 58–100] in children and 73 % [61–88] in young adults for LMS, 100 % [100] vs 92 % [87–99] for M/RC-LPS and 25 % [5–100] vs 60 % [29–100] for pleomorphic LPS. InterpretationLMS and all LPS subtypes appear to display comparable behavior in children and young adults. The authors propose that the same therapeutic strategy should be considered for both groups.

The value of a new diagnostic strategy for adipocytic soft tissue tumors in adults: A retrospective study

IntroductionThe distinction between lipoma and well-differentiated liposarcoma (WDLPS), or “atypical lipomatous tumor” (ALT), is crucial as it impacts patient management. A group of European experts led by Benjamin Moulin recently issued a consensus report to define the role of radiology in managing these lesions. It describes an algorithm defining the criteria prompting a diagnostic biopsy of deep lipomatous tumors of the limbs and chest wall. The primary aim of this study was to evaluate the algorithm's diagnostic performance. Materials and methodsBetween 2012 and 2019, all biopsies of deep fatty tumors of the limbs or chest wall with a pre-biopsy MRI assessment were recorded at our institution. The MRI scans were reviewed by two radiologists. Each lesion was classified according to biopsy status by applying the algorithm of the European panel. The algorithm's diagnostic performance was assessed by calculating the sensitivity, specificity, positive predictive value and negative predictive value. Inter-rater agreement was also assessed. ResultsOf the 156 tumors in our study, 148 (94.9%) required a biopsy, and the algorithm's sensitivity for detecting ALT/WDLPS was 100% with specificity of 6.3% and a PPV of 20.3%. Inter-rater agreement was almost perfect with a kappa value of 0.882. ConclusionThe European algorithm demonstrates perfect sensitivity, an important criterion for a screening examination such as MRI in this setting. The algorithm's low specificity, however, emphasizes the need for further studies to redefine the optimum size cut-off value, especially for lesions without atypical criteria or an anatomical location at risk of post-surgical recurrence.

Diagnostic accuracy of CT and MR features for detecting atypical lipomatous tumors and malignant liposarcomas: a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated the diagnostic accuracy of CT and MRI for differentiating atypical lipomatous tumors and malignant liposarcomas from benign lipomatous lesions. MEDLINE, EMBASE, Scopus, the Cochrane Library, and the gray literature from inception to January 2022 were systematically evaluated. Original studies with > 5 patients evaluating the accuracy of CT and/or MRI for detecting liposarcomas with a histopathological reference standard were included. Meta-analysis was performed using a bivariate mixed-effects regression model. Risk of bias was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). This study is registered on PROSPERO, number CRD42022306479. Twenty-six studies with a total of 2613 patients were included. Mean/median reported patient ages ranged between 50 and 63years. The summary sensitivity and specificity of radiologist gestalt for detecting liposarcomas was 85% (79-90% 95% CI) and 63% (52-72%), respectively. Deep depth to fascia, thickened septations, enhancing components, and lesion size (≥ 10cm) all demonstrated sensitivities ≥ 85%. Other imaging characteristics including heterogenous/amorphous signal intensity, irregular tumor margin, and nodules present demonstrated lower sensitivities ranging from 43 to 65%. Inter-reader reliability for radiologist gestalt within studies ranged from fair to substantial (k = 0.23-0.7). Risk of bias was predominantly mixed for patient selection, low for index test and reference standard, and unclear for flow and timing. Higher sensitivities for detecting liposarcomas were achieved with radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large size. Combined clinical and imaging scoring and/or radiomics both show promise for optimal performance, though require further analysis with prospective study designs. This pooled analysis evaluates the accuracy of CT and MRI for detecting atypical lipomatous tumors and malignant liposarcomas. Radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large size demonstrate the highest overall sensitivities. • The summary sensitivity and specificity of radiologist gestalt for detecting liposarcomas was 85% (79-90% 95% CI) and 63% (52-72%), respectively. • Radiologist gestalt, deep depth to fascia, thickened septations, enhancing components, and large tumor size (≥ 10cm) showed the highest sensitivities for detecting atypical lipomatous tumors/well-differentiated liposarcomas and malignant liposarcomas. • A combined clinical and imaging scoring system and/or radiomics is likely to provide the best overall diagnostic accuracy, although currently proposed scoring systems and radiomic feature analysis require further study with prospective study designs.

MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor of the extremities

PurposeTo determine diagnostic performance of MRI radiomics-based machine learning for classification of deep-seated lipoma and atypical lipomatous tumor (ALT) of the extremities.Material and methodsThis retrospective study was performed at three tertiary sarcoma centers and included 150 patients with surgically treated and histology-proven lesions. The training-validation cohort consisted of 114 patients from centers 1 and 2 (n = 64 lipoma, n = 50 ALT). The external test cohort consisted of 36 patients from center 3 (n = 24 lipoma, n = 12 ALT). 3D segmentation was manually performed on T1- and T2-weighted MRI. After extraction and selection of radiomic features, three machine learning classifiers were trained and validated using nested fivefold cross-validation. The best-performing classifier according to previous analysis was evaluated and compared to an experienced musculoskeletal radiologist in the external test cohort.ResultsEight features passed feature selection and were incorporated into the machine learning models. After training and validation (74% ROC-AUC), the best-performing classifier (Random Forest) showed 92% sensitivity and 33% specificity in the external test cohort with no statistical difference compared to the radiologist (p = 0.474).ConclusionMRI radiomics-based machine learning may classify deep-seated lipoma and ALT of the extremities with high sensitivity and negative predictive value, thus potentially serving as a non-invasive screening tool to reduce unnecessary referral to tertiary tumor centers.

Effectiveness of tumor‑treating fields to reduce the proliferation and migration of liposarcoma cell lines.

Liposarcoma (LPS) is a rare type of soft tissue sarcoma that constitutes 20% of all sarcoma cases in adults. Effective therapeutic protocols for human LPS are not well-defined. Tumor-treating fields (TTFields) are a novel and upcoming field for antitumor therapy. TTFields combined with chemoradiotherapy have proven to be more effective than TTFields combined with radiotherapy or chemotherapy alone. The present study aimed to assess the effectiveness of TTFields in inhibiting cell proliferation and viability for the anticancer treatment of LPS. The present study used TTFields (frequency, 150 kHz; intensity, 1.0 V/cm) to treat two LPS cell lines (94T778 and SW872) and analyzed the antitumor effects. According to trypan blue and MTT assay results, TTFields markedly reduced the viability and proliferation of LPS cell lines along with the formation of colonies in three-dimensional culture. Based on the Transwell chamber assay, TTFields treatment also markedly reduced the migration of LPS cells. Furthermore, as shown by the higher activation of caspase-3 in the Caspase-3 activity assay and the results of the reactive oxygen species (ROS) assay, TTFields increased the formation of ROS in the cells and enhanced the proportion of apoptotic cells. The present study also investigated the inhibitory effect of TTFields in combination with doxorubicin (DOX) on the migratory capacity of tumor cells. The results demonstrated that TTFields treatment synergistically induced the ROS-induced apoptosis of LPS cancer cell lines and inhibited their migratory behavior. In conclusion, the present study demonstrated the potential of TTFields in improving the sensitivity of LPS cancer cells, which may lay the foundation for future clinical trials of this combination treatment strategy.

Phosphorylation of IWS1 by AKT maintains liposarcoma tumor heterogeneity through preservation of cancer stem cell phenotypes and mesenchymal-epithelial plasticity

Chemotherapy remains the mainstay of treatment for patients with advanced liposarcoma (LPS), but response rates are only 25% and the overall survival at 5 years is dismal at 20–34%. Translation of other therapies have not been successful and there has been no significant improvement in prognosis for nearly 20 years. The aberrant activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in the aggressive clinical behavior LPS and in resistance to chemotherapy, but the precise mechanism remains elusive and efforts to target AKT clinically have failed. Here we show that the AKT-mediated phosphorylation of the transcription elongation factor IWS1, promotes the maintenance of cancer stem cells in both cell and xenograft models of LPS. In addition, phosphorylation of IWS1 by AKT contributes to a “metastable” cell phenotype, characterized by mesenchymal/epithelial plasticity. The expression of phosphorylated IWS1 also promotes anchorage-dependent and independent growth, cell migration, invasion, and tumor metastasis. In patients with LPS, IWS1 expression is associated with reduced overall survival, increased frequency of recurrence, and shorter time to relapse after resection. These findings indicate that IWS1-mediated transcription elongation is an important regulator of human LPS pathobiology in an AKT-dependent manner and implicate IWS1 as an important molecular target to treat LPS.

MicroRNA-215-5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2.

Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and it is characterized by dysregulation of multiple signaling pathways, including MDM2 proto-oncogene (MDM2) amplification. MicroRNA (miRNA) regulates gene expression through incomplete complementary pairing with the 3' untranslated region of mRNAs involved in tumor progression. In this study, bioinformatics analysis, RT-qPCR, dual-luciferase reporter gene, MTT, flow cytometry, cell scratches, chamber migration, colony formation, FISH, WB, and CCK8 were used. RT-qPCR showed that the expression of MDM2 was increased when miR-215-5p was overexpressed compared with the control group. The dual-luciferase reporter gene showed that the Renilla ratio firefly fluorescence intensity was decreased in the overexpression group compared with the control group. Cell phenotype experiments revealed that the overexpression group had increased cell proliferation rate, increased apoptosis rate, increased colony formation rate, increased cell healing area ratio, and increased number of cell invasions. FISH revealed increased MDM2 expression in the overexpression group. WB suggested decreased Bax expression, increased PCNA, Bcl-2, and MDM2 expression, and decreased P53 and P21 expression in the overexpression group. In this study, we suggest that miR-215-5p can target and promote MDM2 expression, promote the proliferation and invasion of LPS cells SW-872, and inhibit apoptosis.Targeting miR-215-5p may be a novel therapeutic strategy for the treatment of LPS.

Deciphering the Prognostic and Therapeutic Significance of Cell Cycle Regulator CENPF: A Potential Biomarker of Prognosis and Immune Microenvironment for Patients with Liposarcoma.

Liposarcoma (LPS) is one of the most common subtypes of sarcoma with a high recurrence rate. CENPF is a regulator of cell cycle, differential expression of which has been shown to be related with various cancers. However, the prognostic value of CENPF in LPS has not been deciphered yet. Using data from TCGA and GEO datasets, the expression difference of CENPF and its effects on the prognosis or immune infiltration of LPS patients were analyzed. As results show, CENPF was significantly upregulated in LPS compared to normal tissues. Survival curves illustrated that high CENPF expression was significantly associated with adverse prognosis. Univariate and multivariate analysis suggested that CENPF expression could be an independent risk factor for LPS. CENPF was closely related to chromosome segregation, microtubule binding and cell cycle. Immune infiltration analysis elucidated a negative correlation between CENPF expression and immune score. In conclusion, CENPF not only could be considered as a potential prognostic biomarker but also a potential malignant indicator of immune infiltration-related survival for LPS. The elevated expression of CENPF reveals an unfavorable prognostic outcome and worse immune score. Thus, therapeutically targeting CENPF combined with immunotherapy might be an attractive strategy for the treatment of LPS.

Development and Evaluation of MR-Based Radiogenomic Models to Differentiate Atypical Lipomatous Tumors from Lipomas

The aim of this study was to develop and validate radiogenomic models to predict the MDM2 gene amplification status and differentiate between ALTs and lipomas on preoperative MR images. MR images were obtained in 257 patients diagnosed with ALTs (n = 65) or lipomas (n = 192) using histology and the MDM2 gene analysis as a reference standard. The protocols included T2-, T1-, and fat-suppressed contrast-enhanced T1-weighted sequences. Additionally, 50 patients were obtained from a different hospital for external testing. Radiomic features were selected using mRMR. Using repeated nested cross-validation, the machine-learning models were trained on radiomic features and demographic information. For comparison, the external test set was evaluated by three radiology residents and one attending radiologist. A LASSO classifier trained on radiomic features from all sequences performed best, with an AUC of 0.88, 70% sensitivity, 81% specificity, and 76% accuracy. In comparison, the radiology residents achieved 60-70% accuracy, 55-80% sensitivity, and 63-77% specificity, while the attending radiologist achieved 90% accuracy, 96% sensitivity, and 87% specificity. A radiogenomic model combining features from multiple MR sequences showed the best performance in predicting the MDM2 gene amplification status. The model showed a higher accuracy compared to the radiology residents, though lower compared to the attending radiologist.

Abstract 5993: Dissecting the role of CDK4 in liposarcoma

Abstract Background: Liposarcoma (LPS) encompass one of most common soft tissue sarcoma (STS) histological subtypes accounting for 15% of all cases. They can be divided into four entities including atypical lipomatous tumor or well-differentiated LPS (ALT/WDLPS), dedifferentiated LPS (DDLPS), myxoid LPS (MLPS) and pleomorphic LPS (PLS). Their heterogeneity is reflected in their morphology, molecular landscape, prognosis and clinical behavior. Current treatment options for localized disease include surgery, (neo)adjuvant radiotherapy and chemotherapy; for the metastatic setting chemotherapy represents the cornerstone but its role needs to be elucidated. The unavailability of predictive biomarkers makes the management of these mesenchymal diseases even more challenging. Recent evidences have shed light on the key role of cyclin-dependent kinase 4 (CDK4) in cancer cells proliferation. Methods: This study involved 21 adult patients affected by liposarcoma (n= 5 ALT/WDLPS and n= 16 DDLPS). IHC analyses of CDK4 and MDM2 were performed on FFPE surgically resected specimens by experienced sarcoma pathologists. Moreover, a patient-derived DDLPS cell line was established and pharmacological profiling was performed. Next, standard and innovative drugs currently used for LPS management were assessed in both 2D and 3D culture systems. Finally, in silico analyses based on public repositories on STS were carried out including 260 sarcoma patients. Results: IHC results highlighted an higher expression of CDK4 and MDM2 biomarkers in DDLPS compared to ALT/WDLSP. Moreover, although CDK4 and MDM2 are codified by the same genomic region, their expression did not correlate (e.g. 100% of CDK4 and 2% of MDM2 in the same patient). Therefore we hypothesized that even exhibiting a low MDM2 expression, a patient could benefit from CDK4 inhibition. Furthermore, our data showed that in DDLPS cases CDK4 expression ranged from 90% to 100% in spermatic cord, skin and abdomen while it ranged from 5% to 50% in the retroperitoneum. The above observations prompted us to hypothesize a correlation of CDK4 expression with specific anatomical sites. Moreover, pharmacological profiling showed a synergistic effect exerted by sequential treatment with palbociclib and some chemotherapeutics including trabectedin, dacarbazine, eribulin and lenvatinib. Indeed we observed a 10% increase in cell proliferation inhibition compared to standard treatment. In addition, in silico analyses revealed the role of CDK4 as negative prognostic biomarker for PFS and OS in STS. Conclusions: Our study highlighted the promising role of CDK4 in the management of LPS patients. In particular, we pointed out encouraging results of sequential treatment combining CDK4 inhibitor palbociclib and chemotherapy. Furthermore, preliminary analyses highlighted the involvement of this biomarker as a potential prognostic tool for STS. Citation Format: Silvia Vanni, Graziana Gallo, Valentina Fausti, Giacomo Miserocchi, Chiara Liverani, Chiara Spadazzi, Claudia Cocchi, Chiara Calabrese, Giovanni De Luca, Massimo Bassi, Manlio Gessaroli, Angelo Campobassi, Federica Pieri, Giorgio Ercolani, Davide Cavaliere, Lorena Gurrieri, Nada Riva, Giovanni Martinelli, Laura Mercatali, Alessandro De Vita. Dissecting the role of CDK4 in liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5993.

Abstract 4777: Exploring ferroptosis pathway for the development of therapeutic strategy in liposarcoma

Abstract Background: Liposarcoma (LPS) is one of the most common soft tissue sarcoma (STS) subtypes. Both well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) have 12q13-15 amplification. Mouse double minute 2 homolog (MDM2) is one of the most important oncogenes within this region. Ferroptosis is a unique type of necrotic cell death featured accumulation of lipid-based reactive oxygen species (ROS) derived from the oxidative modification of phospholipid membranes. Cysteine metabolism is the critical part of ferroptosis regulation. Cystine-glutamate antiporter (system xc-; xCT), encoded by two subcomponents, the solute carrier family 7 member 11 (SLC7A11) and SLC3A2, is responsible for cystine supply from extra-cellular environment. Imported cystine is then reduced to cysteine, a key component of tripeptide glutathione (GSH). Glutathione peroxidase 4 (GPX4) requires GSH to repair lipid peroxidation and prevent ferroptosis. Inactivation of GPX4, either through cystine deprivation due to xCT inhibitor erastin, or by GPX4 inhibitor Ras-selective lethal small molecule 3 (RSL3), will lead to accumulation of lipid-based ROS, and eventually ferroptosis cell death. The tumor suppressor p53 (TP53) could suppress the expression of SLC7A11 and induce ferroptosis. TP53 could also indirectly suppress 3-hydroxy-3-methyl-glutaryl (HMG)-coenzyme A (CoA) reductase (HMGCR) activity, a key pathway for generation of biomolecules with anti-ferroptosis property. MDM2, the key oncogene in DDLPS, and homolog MDM4 could facilitate ferroptotic death in TP53-dependent or -independent mechanisms. Methods: We explored public domain database to identify possible aberrations of ferroptosis-related genes in DDLPS. We then examined the sensitivity of DDLPS cell lines to possible ferroptosis-inducing agents. Furthermore, we used nutlin-3, a MDM2 inhibitor, to modulate the MDM2 expression in DDLPS cell line, and explored the potential synergistic effect of nutlin-3 with ferroptosis-inducing agents. Finally, we used immunoblotting study to reveal the potential mechanism responsible to possible synergistic effect. Results: Expression level of GPX4 is significantly lower in DDLPS than adipose tissue and WDLPS, and DPP4 was general higher in LPS than adipose tissue. HMGCR, SLC7A11 and SLC3A2 were mostly up-regulated in LPS in comparison with benign counterpart. Both DDLPS cell lines showed sensitivity to erastin and RSL3. In addition, nutlin-3 could exert synergistic ferroptosis-inducing effect and cytotoxicity with erastin and RSL3 in sequential manner. Furthermore, nultin-3 treatment could upregulate SLC3A2 with altered cystine/glutamate exchange in DDLPS cell lines, indicating possible mechanism responsible for nultin-3 resistance and the synergistic effect of nultin-3 with erastin or RSL3. Conclusion: Our study showed that modulation of ferroptosis is a potential treatment strategy in DDLPS. Citation Format: Chueh-Chuan Yen, San-Chi Chen, Chih-Hsueh Chen, Jir-You Wang, Chao-Ming Chen, Po-Kuei Wu, Muh-Hwa Yang. Exploring ferroptosis pathway for the development of therapeutic strategy in liposarcoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4777.

Evaluation of Classic and Quantitative Imaging Features in the Differentiation of Benign and Atypical Lipomatous Soft Tissue Tumors Using a Standardized Multiparametric MRI Protocol: A Prospective Single-Centre Study in 45 Patients

Discrimination between benign and atypical lipomatous tumors (ALT) is important due to potential local complications and recurrence of ALT but can be difficult due to the often-similar imaging appearance. Using a standardized MRI protocol, this study aimed to rank established and quantitative MRI features by diagnostic value in the differentiation of benign and atypical lipomatous tumors and to develop a robust scoring system. Patients with clinical or sonographic suspicion of a lipomatous tumor were prospectively and consecutively enrolled from 2015 to 2019 after ethic review board approval. Histology was confirmed for all ALT and 85% of the benign cases. Twenty-one demographic and morphologic and twenty-three quantitative features were extracted from a standardized MRI protocol (T1/T2-proton-density-weighting, turbo-inversion recovery magnitude, T2* multi-echo gradient-echo imaging, qDIXON-Vibe fat-quantification, T1 relaxometry, T1 mapping, diffusion-weighted and post-contrast sequences). A ranking of these features was generated through a Bayes network analysis with gain-ratio feature evaluation. Forty-five patients were included in the analysis (mean age, 61.2 ± 14.2 years, 27 women [60.0%]). The highest-ranked ALT predictors were septation thickness (gain ratio merit [GRM] 0.623 ± 0.025, p = 0.0055), intra- and peritumoral STIR signal discrepancy (GRM 0.458 ± 0.046, p < 0.0001), orthogonal diameter (GRM 0.554 ± 0.188, p = 0.0013), contrast enhancement (GRM 0.235 ± 0.015, p = 0.0010) and maximum diameter (GRM 0.221 ± 0.075, p = 0.0009). The quantitative features did not provide a significant discriminatory value. The highest-ranked predictors were used to generate a five-tiered score for the identification of ALTs (correct classification rate 95.7% at a cut-off of three positive items, sensitivity 100.0%, specificity 94.9%, likelihood ratio 19.5). Several single MRI features have a substantial diagnostic value in the identification of ALT, yet a multiparametric approach by a simple combination algorithm may support radiologists in the identification of lipomatous tumors in need for further histological assessment.

Anisometric Cell/Dysplastic Lipomas in a Retinoblastoma Survivor: Report of a Case with Review of the Literature.

Different authors have recently described a subtype of lipoma characterized by variation of adipocyte size, single cell fat necrosis, and a subset with minimal to mild nuclear atypia, and termed these as anisometric cell/dysplastic lipoma (AC/DL). These lipomas follow a benign course and rarely recur. In 3 examples, AC/DL has occurred in patients with childhood retinoblastoma (RB). We report another such example where multiple AC/DL occurred in the neck and back of a 30-year-old male who had germline RB1 gene deletion and bilateral RB in infancy. On excision, all tumors histologically showed similar morphology of adipocyte anisometry, focal single cell necrosis with surrounding binucleated or multinucleated histiocytes, hyperchromatic and minimally atypical lipocyte nuclei, vacuolated Lockhern change, rare foci of fibromyxoid change, occasional mononuclear cell clusters around capillaries, and loss of RB1 immunostaining. Unequivocal atypical cells, lipoblasts, floret-nucleated or multinucleated giant cells were absent. Molecular analysis of tumor cells showed monoallelic RB1 gene loss without amplification of MDM2 and CDK4 genes. Short-term follow up did not show tumor recurrence. AC/DLs in RB survivors are characterized by multiplicity, unifying histology, and benign course. Their biology appears distinct from ordinary lipomas, spindle cell lipomas, and atypical lipomatous tumors.

Prognostic factors and outcomes of adult spermatic cord sarcoma. A study from the French Sarcoma Group

PurposeTo evaluate the outcomes of adult patients with spermatic cord sarcoma (SCS). MethodsAll consecutive patients with SCS managed by the French Sarcoma Group from 1980 to 2017 were analysed retrospectively. Multivariate analysis (MVA) was used to identify independent correlates of overall survival (OS), metastasis-free survival (MFS), and local relapse-free survival (LRFS). ResultsA total of 224 patients were recorded. The median age was 65.1 years. Forty-one (20.1%) SCSs were discovered unexpectedly during inguinal hernia surgery. The most common subtypes were liposarcoma (LPS) (73%) and leiomyosarcoma (LMS) (12.5%). The initial treatment was surgery for 218 (97.3%) patients. Forty-two patients (18.8%) received radiotherapy, 17 patients (7.6%) received chemotherapy. The median follow-up was 5.1 years. The median OS was 13.9 years. In MVA, OS decreased significantly with histology (HR, well-differentiated LPS versus others = 0.096; p = 0.0224), high grade (HR, 3 versus 1–2 = 2.7; p = 0.0111), previous cancer and metastasis at diagnosis (HR = 6.8; p = 0.0006). The five-year MFS was 85.9% [95% CI: 79.3–90.6]. In MVA, significant factors associated with MFS were LMS subtype (HR = 4.517; p < 10-4) and grade 3 (HR = 3.664; p < 10-3). The five-year LRFS survival rate was 67.9% [95% CI: 59.6–74.9]. In MVA, significant factors associated with local relapse were margins and wide reresection (WRR) after incomplete resection. OS was not significantly different between patients with initial R0/R1 resection and R2 patients who underwent WRR. ConclusionsUnplanned surgery affected 20.1% of SCSs. A nonreducible painless inguinal lump should suggest a sarcoma. WRR with R0 resection achieved similar OS to patients with correct surgery upfront.

Oncology

The February 2023 Oncology Roundup360 looks at: Is the number of national database research studies in musculoskeletal sarcoma increasing, and are these studies reliable?; Re-excision after unplanned excision of soft-tissue sarcoma is associated with high morbidity; Adjuvant radiation in atypical lipomatous tumours; The oncological outcomes of isolated limb perfusion and neoadjuvant radiotherapy in soft-tissue sarcoma patients - a nationwide multicentre study; Can low-grade chondrosarcoma be treated with intralesional curettage and cryotherapy?; Efficacy and safety of carbon ion radiotherapy for bone sarcomas: a systematic review and meta-analysis; Doxorubicin-polymeric meshes prevent local recurrence after sarcoma resection while avoiding cardiotoxicity; How important are skip lesions in Ewing’s sarcoma?; Improving outcomes for amputees: the health-related quality of life and cost utility analysis of osseointegration prosthetics in transfemoral amputees.

Silver In Situ Hybridization for the Rapid Assessment of MDM2 Amplification in Soft Tissue and Bone Tumors. Validation Based on an Audit of 192 Consecutive Cases Evaluated by Silver In Situ Hybridization and Fluorescence In Situ Hybridization.

The discovery of almost invariable mouse double minute 2 (MDM2) amplification among atypical lipomatous tumors (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma is incorporated into the contemporary diagnostic workup of fatty lesions. MDM2 amplifications are also found frequently in intimal sarcomas and in low-grade osteogenic sarcoma. At present, fluorescence in situ hybridization (FISH) is the reference test for MDM2 assessment. We are interested in evaluating silver in situ hybridization (SISH) for this purpose. Between October 2016 and May 2020, in 192 consecutive cases requiring MDM2 FISH, SISH was also performed concurrently, including 77 (40.1%) core biopsies and 115 (58.9%) surgical specimens. The mean patient age was 61.0 years. SISH results were available overnight or within 48 hours if repeat testing was required. FISH results were available within 2 to 5 weeks. The cost of SISH was one third of FISH. FISH demonstrated MDM2 amplification in 44 cases (23.6%), was negative in 144 cases (74.4%) and nondiagnostic in 4 decalcified cases (2.0%). SISH showed MDM2 amplification in 33 cases (17.2%), no amplification in 119 cases (62.0%), and indeterminate results because of poor signal in 40 (20.8%) cases. All 33 (100%) SISH-amplified tumors and 113 of 119 (95.0%) nonamplified results were confirmed by FISH. There were no clear differences in the performance of SISH on NCB versus surgical specimens. The overall performance indices of SISH are sensitivity 75%, specificity 78.5%, positive predictive value 100%, and negative predictive value 95.8%. FISH is not required when SISH is clearly amplified. This is clinically useful and improves efficiency. Nonamplified SISH results provide early indications of the likely FISH findings, but there is a 4.2% chance of FISH being positive. At present, the main drawback of SISH is the high rate of nondiagnostic tests. Optimization of SISH signal detection to reduce the proportion of indeterminate results is our current focus.

FISH Diagnostic Assessment of MDM2 Amplification in Liposarcoma: Potential Pitfalls and Troubleshooting Recommendations.

MDM2 amplification represents the leading oncogenic pathway and diagnostic hallmark of liposarcoma, whose assessment is based on Fluorescence In Situ Hybridization (FISH) analysis. Despite its diagnostic relevance, no univocal interpretation criteria regarding FISH assessments of MDM2 amplification have been established so far, leading to several different approaches and potential diagnostic misinterpretations. This study aims to address the most common issues and proposes troubleshooting guidelines for MDM2 amplification assessments by FISH. We retrospectively retrieved 51 liposarcomas, 25 Lipomas, 5 Spindle Cell Lipoma/Pleomorphic Lipomas, and 2 Atypical Spindle Cell Lipomatous Tumors and the corresponding MDM2 FISH analysis. We observed MDM2 amplification in liposarcomas cases only (43 out of 51 cases) and identified three MDM2-amplified patterns (scattered (50% of cases), clustered (14% of cases), and mixed (36% of cases)) and two nonamplified patterns (low number of signals (82% of cases) and polysomic (18% of cases)). Based on these data and published evidence in the literature, we propose a set of criteria to guide MDM2 amplification analysis in liposarcoma. Kindled by the compelling importance of MDM2 assessments to improve diagnostic and therapeutic liposarcoma management, these suggestions could represent the first step to develop a univocal interpretation model and consensus guidelines.

Intraoral lipoma with degenerative changes mimicking atypical lipomatous tumor: an immunohistochemical study

Lipomas are mesenchymal neoplasms relatively uncommon in the oral cavity. Lipomas can exhibit histopathological features mimicking atypical lipomatous tumors (ALT) or dysplastic lipoma (DL) in the presence of degenerative changes. Relevantly, immunohistochemistry assists in the correct diagnosis. Herein, we present the case of a 54-year-old male with a sessile nodule located on the dorsum of the tongue. The histopathological analysis showed a diffuse, non-circumscribed adipocytic proliferation constituted by cells of variable size containing cytoplasmic vacuoles and displaced nuclei, some resembling lipoblasts supported by fibrous connective tissue stroma. By immunohistochemistry, tumor cells were positive for vimentin, S100, FASN, CD10, and p16. Rb expression was intact. Moreover, CD34, p53, MDM2, and CDK4 were negative. After 2-year of follow-up, no alteration or recurrence was observed. In conclusion, MDM2, CDK4, p53, and Rb immunomarkers can be used reliably to differentiate benign lipoma with degenerative changes from ALT and DL.

Well-Differentiated Liposarcoma as a Case: The Competence of Surgical Treatment was Questioned

Sarcomas are malignant tumors arising from skeletal and non-skeletal connective tissue, as well as the peripheral nervous system. Sarcoma is detected in the majority of patients who have a primary retroperitoneal, extra-visceral, unifocal soft tissue mass. Liposarcoma and leiomyosarcoma are the most prevalent histologic types of retroperitoneal sarcoma in adults. Most retroperitoneal liposarcomas are known as low to mild grade tumors. Well differentiated (low grade) liposarcomas are the most prevalent kind and have no potential to metastasize. Atypical lipomatous tumors are defined as those that develop on the body wall, trunk, or extremity. However, the same tumors are called well-differentiated liposarcomas due to their tendency for local recurrence and located in the retroperitoneum, mediastinum, and spermatic cord. In our case, we aimed to present a case that occupies most of the intra-abdominal volume, has associated gastrointestinal system complaints, and eventually was diagnosed as well-differentiated liposarcoma following surgical treatment.

Giemsa staining proved useful for fine-needle aspiration cytology of an atypical lipomatous tumor arising in the subcutaneous tissue of the left upper neck

Giemsa staining proved useful for fine-needle aspiration cytology of an atypical lipomatous tumor arising in the subcutaneous tissue of the left upper neck