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1.
Rev. esp. patol ; 57(2): 128-132, Abr-Jun, 2024. ilus
Article En | IBECS | ID: ibc-232418

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification. (AU)


El liposarcoma hepático primario es un tumor maligno extremadamente raro, derivado de adipocitos, y forma parte del grupo de tumores mesenquimales. Presentamos el caso de un paciente masculino de 43 años con diagnóstico de liposarcoma hepático pleomorfo con ausencia de amplificación del gen MDM2. Dos años y 6 meses después de la cirugía el paciente se encuentra asintomático. El presente caso es el primer informe de esta entidad con estudio inmunohistoquímico positivo para p16, p53, S100, vimentina y ausencia de amplificación del gen MDM2. (AU)


Humans , Male , Adult , Liposarcoma , Neoplasms , Adipocytes , Mesenchymal Stem Cells , Vimentin
3.
World J Surg Oncol ; 22(1): 131, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760830

BACKGROUND: Liposarcomas are among the most common mesenchymal malignancies. However, the therapeutic options are still very limited and so far, targeted therapies had not yet been established. Immunotherapy, which has been a breakthrough in other oncological entities, seems to have no efficacy in liposarcoma. Complicating matters further, classification remains difficult due to the diversity of morphologies and nonspecific or absent markers in immunohistochemistry, leaving molecular pathology using FISH or sequencing as best options. Many liposarcomas harbor MDM2 gene amplifications. In close relation to the gene locus of MDM2, HER3 (ERBB3) gene is present and co-amplification could occur. Since the group of HER/EGFR receptor tyrosine kinases and its inhibitors/antibodies play a role in a broad spectrum of oncological diseases and treatments, and some HER3 inhibitors/antibodies are already under clinical investigation, we hypothesized that in case of HER3 co-amplifications a tumor might bear a further potential therapeutic target. METHODS: We performed FISH analysis (MDM2, DDIT3, HER3) in 56 archived cases and subsequently performed reclassification to confirm the diagnosis of liposarcoma. RESULTS: Next to 16 out of 56 cases needed to be re-classified, in 20 out of 54 cases, a cluster-amplification of HER3 could be detected, significantly correlating with MDM2 amplification. Our study shows that the entity of liposarcomas show specific molecular characteristics leading to reclassify archived cases by modern, established methodologies. Additionally, in 57.1% of these cases, HER3 was cluster-amplified profusely, presenting a putative therapeutic target for targeted therapy. CONCLUSION: Our study serves as the initial basis for further investigation of the HER3 gene as a putative therapeutic target in liposarcoma.


Gene Amplification , Liposarcoma , Proto-Oncogene Proteins c-mdm2 , Receptor, ErbB-3 , Humans , Liposarcoma/genetics , Liposarcoma/pathology , Liposarcoma/metabolism , Receptor, ErbB-3/genetics , Receptor, ErbB-3/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , In Situ Hybridization, Fluorescence , Female , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Male , Prognosis , Middle Aged , Aged , Molecular Targeted Therapy/methods , Adult
4.
Acta Ortop Mex ; 38(2): 113-118, 2024.
Article En | MEDLINE | ID: mdl-38782478

INTRODUCTION: conventional parosteal osteosarcoma is an uncommon malignant bone tumor, comprising 4% of all osteosarcomas. Although rare, parosteal osteosarcoma is the most common type of osteosarcoma of the bone surface. We present the clinical, histological and imaging characteristics of a rare histologic variant of a parosteal osteosarcoma, review the literature and emphasize the importance of radio-pathological correlation as well as the interpretation of a representative biopsy in order to obtain the correct diagnosis. CASE REPORT: a 36-year old woman began her condition one year prior to admission to the hospital with increased volume in the left knee and pain. Image studies showed a juxtacortical heterogeneous tumor localized on the posterior surface of the distal femoral metaphysis. An incisional biopsy was performed, with the diagnosis of a Parosteal Osteosarcoma and a wide surgical resection was undertaken. According to the findings of the surgical specimen, the diagnosis of a Parosteal Osteosarcoma with low grade chondrosarcoma and liposarcoma components was made. The knowledge of this rare parosteal osteosarcoma variant can lead the orthopedic oncologists to avoid overlooking the adipose component and provide adequate surgical margins. CONCLUSION: we present the clinical, histological and imaging characteristics of a Parosteal Osteosarcoma with low grade liposarcoma and chondrosarcoma components.


INTRODUCCIÓN: el osteosarcoma parosteal convencional es un tumor óseo maligno poco común, que comprende el 4% de todos los osteosarcomas. Aunque es poco común, el osteosarcoma parosteal es el tipo más común de osteosarcoma de la superficie ósea. Presentamos las características clínicas, histológicas y de imagen de una variante histológica rara de un osteosarcoma parosteal, revisamos la literatura y enfatizamos la importancia de la correlación radio-patológica, así como la interpretación de una biopsia representativa para obtener el diagnóstico correcto. REPORTE DE CASO: mujer de 36 años inició su cuadro un año antes de su ingreso al hospital con aumento de volumen en rodilla izquierda y dolor. Los estudios de imagen mostraron una tumoración heterogénea yuxtacortical localizada en la superficie posterior de la metáfisis femoral distal. Se realizó biopsia incisional, con diagnóstico de osteosarcoma parosteal y se realizó resección quirúrgica amplia. De acuerdo con los hallazgos de la pieza quirúrgica se realizó el diagnóstico de osteosarcoma parosteal con componentes de condrosarcoma y liposarcoma de bajo grado. El conocimiento de esta rara variante de osteosarcoma parosteal puede llevar a los ortopedistas oncólogos a considerar otros componentes y proporcionar márgenes quirúrgicos adecuados. CONCLUSIÓN: presentamos las características clínicas, histológicas y de imagen de un osteosarcoma parosteal con componentes de liposarcoma y condrosarcoma de bajo grado.


Chondrosarcoma , Liposarcoma , Osteosarcoma, Juxtacortical , Humans , Female , Adult , Liposarcoma/pathology , Liposarcoma/surgery , Liposarcoma/diagnosis , Chondrosarcoma/pathology , Chondrosarcoma/surgery , Chondrosarcoma/diagnosis , Osteosarcoma, Juxtacortical/pathology , Osteosarcoma, Juxtacortical/diagnosis , Osteosarcoma, Juxtacortical/surgery , Femoral Neoplasms/pathology , Femoral Neoplasms/surgery , Femoral Neoplasms/diagnostic imaging , Femoral Neoplasms/diagnosis , Bone Neoplasms/pathology , Bone Neoplasms/surgery , Bone Neoplasms/diagnosis
5.
Sci Rep ; 14(1): 11254, 2024 05 16.
Article En | MEDLINE | ID: mdl-38755218

Dedifferentiated liposarcoma (DDLS) is an aggressive, recurring sarcoma with limited treatments. T-cell immunotherapies selectively target malignant cells, holding promise against DDLS. The development of successful immunotherapy for DDLS requires a thorough evaluation of the tumor immune microenvironment and the identification and characterization of targetable immunogenic tumor antigens. To assess the complexity of the human DDLS tumor immune microenvironment and to identify target antigens, we used the nCounter NanoString platform, analyzing gene expression profiles across 29 DDLS and 10 healthy adipose tissue samples. Hierarchical clustering of tumors based on expression of tumor inflammation signature genes revealed two distinct groups, consisting of 15 inflamed tumors and 14 non-inflamed tumors, demonstrating tumor heterogeneity within this sarcoma subtype. Among the identified antigens, PBK and TTK exhibited substantial upregulation in mRNA expression compared to healthy adipose tissue controls, further corroborated by positive protein expression by IHC. This data shows considerable inter-tumoral heterogeneity of inflammation, which should be taken into consideration when designing an immunotherapy for DDLS, and provides a novel targetable antigen in DDLS. The results of this study lay the groundwork for the development of a novel immunotherapy for this highly aggressive sarcoma.


Antigens, Neoplasm , Immunotherapy , Liposarcoma , Humans , Liposarcoma/immunology , Liposarcoma/genetics , Liposarcoma/therapy , Liposarcoma/pathology , Immunotherapy/methods , Antigens, Neoplasm/immunology , Antigens, Neoplasm/genetics , Male , Female , Middle Aged , Aged , Tumor Microenvironment/immunology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Adult
6.
J Mol Histol ; 55(3): 227-240, 2024 Jun.
Article En | MEDLINE | ID: mdl-38696048

Liposarcoma (LPS) is a rare malignancy of adipocytic differentiation. According to World Health Organization classification, LPS comprises of four principle subtypes Atypical lipomatous tumor/Well-differentiated liposarcoma (ATL/WDLPS), Dedifferentiated liposarcoma (WDLPS), Myxoid liposarcoma (MLPS), and Pleomorphic liposarcoma (PLPS). Each subtype can develop at any location and shows distinct clinical behavior and treatment sensitivity. ATL/ WDLPS subtype has a higher incidence rate, low recurrence, and is insensitive to radiation and chemotherapy. DDLPS is the focal progression of WDLPS, which is aggressive and highly metastasizing. MLPS is sensitive to radiation and chemotherapy, with a higher recurrence rate and metastasis. PLPS subtype is highly metastasizing, has a poor prognosis, and exhibiting higher recurrence rate. Initial histological analysis provides information for the characterization of LPS subtypes', further molecular and genetic analysis provides certain subtype specifications, such as gene amplifications and gene fusions. Such molecular genetic alterations will be useful as therapeutic targets in various cancers, including the LPS subtypes. A wide range of novel therapeutic agents based on genetic alterations that aim to target LPS subtypes specifically are under investigation. This review summarizes the LPS subtype classification, their molecular genetic characteristics, and the implications of genetic alterations in therapeutics.


Liposarcoma , Humans , Liposarcoma/genetics , Liposarcoma/therapy , Liposarcoma/pathology , Liposarcoma/diagnosis , Liposarcoma/classification
7.
Commun Biol ; 7(1): 606, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769442

Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.


Gene Amplification , Liposarcoma , Proto-Oncogene Proteins c-mdm2 , Humans , Liposarcoma/genetics , Liposarcoma/pathology , Proto-Oncogene Proteins c-mdm2/genetics , Chromosomes, Human, Pair 12/genetics , Chromothripsis , Ring Chromosomes
8.
Surg Oncol ; 54: 102074, 2024 Jun.
Article En | MEDLINE | ID: mdl-38615387

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.


Leiomyosarcoma , Liposarcoma , Humans , Leiomyosarcoma/surgery , Leiomyosarcoma/pathology , Leiomyosarcoma/mortality , Liposarcoma/surgery , Liposarcoma/pathology , Liposarcoma/mortality , Male , Female , Survival Rate , Prognosis , Middle Aged , Aged , Pelvic Neoplasms/surgery , Pelvic Neoplasms/pathology , Pelvic Neoplasms/mortality , Follow-Up Studies , Retrospective Studies
9.
World J Surg ; 48(1): 97-103, 2024 Jan.
Article En | MEDLINE | ID: mdl-38686806

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.


Liposarcoma , Marital Status , Pelvic Neoplasms , Humans , Male , Liposarcoma/mortality , Female , Middle Aged , Marital Status/statistics & numerical data , Aged , Pelvic Neoplasms/mortality , Sex Factors , SEER Program , Adult , Retrospective Studies
10.
Anticancer Res ; 44(5): 2125-2132, 2024 May.
Article En | MEDLINE | ID: mdl-38677749

BACKGROUND/AIM: Trabectedin is used as a treatment for advanced-stage soft tissue sarcomas (STSs), particularly liposarcoma and leiomyosarcoma. Aside from its direct effect on tumor cells, trabectedin can affect the immune system in the tumor microenvironment. This study aimed to evaluate whether inflammatory biomarkers predict trabectedin efficacy in STSs. PATIENTS AND METHODS: We retrospectively reviewed the clinical features and outcomes of patients with STS treated with trabectedin at our institution between 2016 and 2020. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI=neutrophil × monocyte/lymphocyte) were calculated based on the blood samples obtained prior to trabectedin treatment initiation. Analyses of overall survival (OS) and progression-free survival (PFS) were performed according to various factors. RESULTS: Of the 101 patients identified, 54 had L-sarcoma (leiomyosarcoma: 30; liposarcoma: 24), and 47 had other types of STSs. Elevated SIRI, NLR, PLR, LMR, and C-reactive protein (CRP) were associated with worse PFS (p<0.001, p=0.008, p=0.027, p=0.013, and p<0.001, respectively) according to the results of the univariate analysis. Multivariate analysis showed that elevated SIRI, other histology, and CRP were associated with poor PFS (p=0.007, p=0.008, and p=0.029, respectively). In addition, the multivariate analysis of OS showed that SIRI was an independent prognostic factor (hazard ratio=2.16, p=0.006). CONCLUSION: Pretreatment SIRI can be considered a biomarker for the prognostic prediction of patients with STS treated with trabectedin.


Sarcoma , Trabectedin , Humans , Trabectedin/therapeutic use , Female , Male , Middle Aged , Aged , Sarcoma/drug therapy , Sarcoma/pathology , Sarcoma/blood , Adult , Retrospective Studies , Antineoplastic Agents, Alkylating/therapeutic use , Biomarkers, Tumor/blood , Aged, 80 and over , Lymphocytes/pathology , Inflammation/drug therapy , Inflammation/blood , Inflammation/pathology , Neutrophils/pathology , Prognosis , Young Adult , Progression-Free Survival , Monocytes/pathology , Treatment Outcome , Liposarcoma/drug therapy , Liposarcoma/pathology , Liposarcoma/blood
12.
BMJ Case Rep ; 17(4)2024 Apr 16.
Article En | MEDLINE | ID: mdl-38627046

A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.


Genital Neoplasms, Male , Lipoma , Liposarcoma, Myxoid , Liposarcoma , Spermatic Cord , Male , Animals , Mice , Humans , Adult , Spermatic Cord/pathology , Lipopolysaccharides , Liposarcoma/pathology , Liposarcoma, Myxoid/pathology , Lipoma/pathology , Pain , Genital Neoplasms, Male/pathology
13.
Folia Histochem Cytobiol ; 62(1): 50-60, 2024.
Article En | MEDLINE | ID: mdl-38639334

INTRODUCTION: Liposarcoma constitutes a prevalent subtype of soft tissue sarcoma, represents approximately 20% of all sarcomas. However, conventional chemotherapeutic agents have shown restricted effectiveness in treating liposarcoma patients. Accumulating evidence indicates that mesenchymal stem cells (MSCs) have the characteristic of migration to tumor site, promote or suppress tumors. How human bone marrow mesenchymal stem cells (BMSCs) contribute to liposarcoma phenotype remains poorly understood. This study aims to investigate the effects of human bone marrow mesenchymal stem cell-conditioned medium (BMSC-CM) on the proliferation and migration of liposarcoma cell lines 93T449 and SW872, as well as explore potential underlying mechanisms of BMSC-CM action on these cells. MATERIALS AND METHODS: We transfected BMSCs with lentiviral constructs to knock down the transcriptional co-activator Yes-associated protein 1 (YAP1), conditioned medium (CM) obtained from BMSCs and shYAP1-BMSC, respectively. Liposarcoma cell lines 93T449 and SW872 were co-cultured with BMSC-CM or shYAP1-BMSC-CM. Cell proliferation ability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was evaluated using flow cytometric assay. A wound healing assay was used to analyze cell migration. The expression levels of YAP1, Bcl-2, and matrix metalloproteinase-2 (MMP-2) were determined by western blot assay. RESULTS: Co-culturing liposarcoma cell lines 93T449 and SW872 with BMSC-CM promoted tumor cell proliferation, while shYAP1-BMSC-CM significantly inhibited cell viability and migration, induced apoptosis, and downregulated Bcl-2 and MMP-2 expression. CONCLUSIONS: These findings provide new insights into the impact of BMSC-CM on liposarcoma and suggest its possible involvement in liposarcoma cell growth.


Liposarcoma , Mesenchymal Stem Cells , Humans , Matrix Metalloproteinase 2/metabolism , Culture Media, Conditioned/pharmacology , Culture Media, Conditioned/metabolism , Liposarcoma/metabolism , Cell Proliferation , Mesenchymal Stem Cells/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Bone Marrow Cells/metabolism
14.
Rev Esp Patol ; 57(2): 128-132, 2024.
Article En | MEDLINE | ID: mdl-38599733

Primary hepatic liposarcoma is an extremely rare malignant tumour derived from adipocytes and is part of the group of mesenchymal tumours. We present the case of a 43-year-old Hispanic male patient with a pleomorphic hepatic liposarcoma and absence of MDM2 gene amplification. Two years and six months after surgery, the patient is asymptomatic. The present case is the first report of this entity with positive immunohistochemical testing for p16, p53, S100, vimentin and absence of MDM2 gene amplification.


Liposarcoma , Proto-Oncogene Proteins c-mdm2 , Humans , Male , Adult , Proto-Oncogene Proteins c-mdm2/genetics , Liposarcoma/pathology , Adipocytes/pathology
15.
Radiat Oncol ; 19(1): 38, 2024 Mar 16.
Article En | MEDLINE | ID: mdl-38491404

BACKGROUND: The addition of radiation therapy (RT) to surgery in retroperitoneal sarcoma (RPS) remains controversial. We examined practice patterns in the use of RT for patients with RPS over time in a large, national cohort. METHODS: Patients in the National Cancer Database (2004-2017) who underwent resection of RPS were included. Trends over time for proportions were calculated using contingency tables with Cochran-Armitage Trend test. RESULTS: Of 7,485 patients who underwent resection, 1,821 (24.3%) received RT (adjuvant: 59.9%, neoadjuvant: 40.1%). The use of RT decreased annually by < 1% (p = 0.0178). There was an average annual increase of neoadjuvant RT by 13% compared to an average annual decrease of adjuvant RT by 6% (p < 0.0001). Treatment at high-volume centers (OR 14.795, p < 0.0001) and tumor > 10 cm (OR 2.009, p = 0.001) were associated with neoadjuvant RT. In contrast liposarcomas (OR 0.574, p = 0.001) were associated with adjuvant RT. There was no statistically significant difference in overall survival between patients treated with surgery alone versus surgery and RT (p = 0.07). CONCLUSION: In the United States, the use of RT for RPS has decreased over time, with a shift towards neoadjuvant RT. However, a large percentage of patients are still receiving adjuvant RT and this mostly occurs at low-volume hospitals.


Liposarcoma , Retroperitoneal Neoplasms , Sarcoma , Soft Tissue Neoplasms , Humans , United States , Radiotherapy, Adjuvant/adverse effects , Sarcoma/radiotherapy , Sarcoma/surgery , Combined Modality Therapy , Retroperitoneal Neoplasms/radiotherapy , Retroperitoneal Neoplasms/surgery , North America , Retrospective Studies
16.
Kyobu Geka ; 77(3): 230-234, 2024 Mar.
Article Ja | MEDLINE | ID: mdl-38465498

A 61-year-old woman was referred for further evaluation of an intracystic nodule in her left upper lung. Computed tomography( CT) showed a 15 mm nodule in a pulmonary cyst adjacent to aortic arch and mediastinum. Fluorodeoxyglucose-positron emission tomography (FDG-PET)-CT showed little uptake of FDG in the lesion. No abnormality was found in the bronchoscopy findings. On imaging findings, the possibility of pulmonary aspergilloma was considered, but the serological findings were inconsistent, and surgical resection of the lesion was performed for both diagnosis and treatment. The final pathohistological diagnosis was well differentiated liposarcoma. No adjuvant therapy was performed and the patient has been well without recurrence for 2 years after the surgery. We report a rare case of well differentiated liposarcoma of a lung mimicking pulmonary aspergilloma.


Lipoma , Liposarcoma , Pulmonary Aspergillosis , Humans , Female , Middle Aged , Fluorodeoxyglucose F18 , Positron-Emission Tomography , Lung , Tomography, X-Ray Computed , Liposarcoma/diagnostic imaging , Liposarcoma/surgery
17.
Eur J Cancer ; 202: 114005, 2024 May.
Article En | MEDLINE | ID: mdl-38531265

INTRODUCTION: Dedifferentiated liposarcoma (DDLPS) is a common form of liposarcoma with challenging treatment modalities. Pan-TRK immunopositivity can be often observed without NTRK gene fusion in soft tissue sarcomas with myogenic differentiation. Expression and the role of NTRK in DDLPS are under-studied. We sought to identify activating mutations of the NTRK genes. MATERIALS AND METHODS: 131 DDLPS patients were selected for pan-TRK immunohistochemistry and positive cases were analyzed by Sanger sequencing for NTRK1, NTRK2 and NTRK3 genes. Functional assays were performed using a lentiviral transduction system to study the effect of NTRK variants in fibroblast, immortalized fibroblast, and dedifferentiated liposarcoma cell lines. RESULTS: Out of the 131 DDLPS cases, 75 immunohistochemical staining positive cases, 46 were successfully Sanger sequenced. A recurrent somatic mutation pair in cis position (NGS) of the NTRK1 c.1810C>T (p.H604Y) and c.1838G>T (p.G613V) was identified in six cases (13%) that have never been reported in DDLPS. NTRK fusions were excluded in all six cases by FISH and NGS. The phospho-AKT immunopositivity among the six mutated cases suggested downstream activation of the NTRK signaling pathway. Functional assays showed no transforming effects, but resistance to first- and second-line TRK inhibitors of the p.G613V and p.H604Y variant. CONCLUSIONS: We detected (de novo/somatic) missense mutation variants in cis position of the NTRK1 gene in a subset of DDLPS indicating modifying mutations that may contribute to tumorigenesis in a subset of DDLPS. These variants beget resistance to TRK inhibitors indicating an interesting biomarker for other studies with TRK inhibitors.


Liposarcoma , Sarcoma , Soft Tissue Neoplasms , Humans , Liposarcoma/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Receptor, trkA/genetics , Sarcoma/genetics , Soft Tissue Neoplasms/genetics
18.
Medicine (Baltimore) ; 103(13): e37604, 2024 Mar 29.
Article En | MEDLINE | ID: mdl-38552050

RATIONALE: Retroperitoneal dedifferentiated liposarcoma (RPDDL) is an uncommon malignancy, which often remains undetected for many years due to having adequate space in the retroperitoneal cavity and lacking clinical manifestations in the early stage of the disease. Surgical procedure is usually used as the first choice for treatment. However, it is prone to local recurrence after the operation, resulting in an unfavorable prognosis. Our aim is to draw useful lessons from the new case and provide some experience for management of the disease. PATIENT CONCERNS: We describe a 55-year-old male patient who was admitted for a 3-week history of persistent dull ache of the left waist. A large mass of the left upper abdomen was palpated in physical examination. Moreover, the imaging examination revealed that the diameter of the mass was about 21 cm, and some adjacent vital organs were invaded, which brought great challenges to complete surgical resection. DIAGNOSIS: The postoperative pathological results confirmed that the mass was RPDDL with invasion of the surrounding vital structures including pancreas, spleen, left adrenal gland, left kidney, and vasculature with tumor emboli. INTERVENTIONS: Surgical resection of the mass was performed by our multidisciplinary team. The patient received chemotherapy 1 month after surgery. OUTCOMES: The effect of chemotherapy seemed to be unsatisfactory. Local multifocal recurrence of the tumor was considered about 2 months after surgery. Finally, he gave up any treatments and died of the disease. LESSONS: Regular physical examination and ultrasound screening may detect the disease as early as possible, especially for high-risk group aged 60 to 70, which should be popularized. Incomplete resection, vascular invasion, and interruption of postoperative treatment may lead to an unfavorable prognosis. Therefore, we think that patients with the disease may benefit from complete surgical resection and uninterrupted adjuvant therapy.


Liposarcoma , Retroperitoneal Neoplasms , Male , Humans , Middle Aged , Retroperitoneal Neoplasms/diagnostic imaging , Retroperitoneal Neoplasms/surgery , Retroperitoneal Neoplasms/pathology , Retroperitoneal Space/pathology , Liposarcoma/diagnostic imaging , Liposarcoma/surgery , Liposarcoma/pathology , Kidney/pathology
20.
Zhonghua Wai Ke Za Zhi ; 62(5): 472-476, 2024 May 01.
Article Zh | MEDLINE | ID: mdl-38548619

Retroperitoneal liposarcoma is the most common retroperitoneal soft tissue tumor with insidious onset, difficulty in treatment, and easy recurrence. Different subtypes of retroperitoneal liposarcoma differ significantly in pathogenic mechanism, biological behavior, and prognosis. The characteristic molecular event of well-differentiated and dedifferentiated liposarcoma is the amplification of the long arm segment of chromosome 12. The genome of myxoid liposarcoma is characterized by translocations of chromosomes 12 and 16 to form fusion genes. The genomic changes of pleomorphic and myxoid pleomorphic liposarcoma are complex, with multiple chromosomal structural abnormalities. Several signaling pathways related to adipocyte differentiation or lipid metabolism have been found to be involved in the initiation and progression of retroperitoneal liposarcoma. It is unclear whether retroperitoneal liposarcoma originates from naive preadipocytes or dedifferentiated mature adipocytes, and its metabolic characteristics are also poorly understood. The first-line drug treatment for retroperitoneal liposarcoma is anthracycline-based chemotherapy, but patients receive little benefit. Therefore, it is urgent to strengthen the basic research on retroperitoneal liposarcoma to find effective therapeutic targets.


Liposarcoma , Retroperitoneal Neoplasms , Humans , Liposarcoma/genetics , Retroperitoneal Neoplasms/genetics , Retroperitoneal Neoplasms/pathology
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