-
Journal of Clinical Oncology : Official... Jan 2018Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical... (Review)
Review
Liposarcomas are rare malignant tumors of adipocytic differentiation. The classification of liposarcomas into four principal subtypes reflects the distinct clinical behavior, treatment sensitivity, and underlying biology encompassed by these diseases. Increasingly, clinical management decisions and the development of investigational therapeutics are informed by an improved understanding of subtype-specific molecular pathology. Well-differentiated liposarcoma is the most common subtype and is associated with indolent behavior, local recurrence, and insensitivity to radiotherapy and chemotherapy. Dedifferentiated liposarcoma represents focal progression of well-differentiated disease into a more aggressive, metastasizing, and fatal malignancy. Both of these subtypes are characterized by recurrent amplifications within chromosome 12, resulting in the overexpression of disease-driving genes that have been the focus of therapeutic targeting. Myxoid liposarcoma is characterized by a pathognomonic chromosomal translocation that results in an oncogenic fusion protein, whereas pleomorphic liposarcoma is a karyotypically complex and especially poor-prognosis subtype that accounts for less than 10% of liposarcoma diagnoses. A range of novel pharmaceutical agents that aim to target liposarcoma-specific biology are under active investigation and offer hope of adding to the limited available treatment options for recurrent or inoperable disease.
Topics: Adipocytes; Cell Differentiation; Chemoradiotherapy; Chromosome Aberrations; Humans; Immunotherapy; Liposarcoma; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Outcome Assessment, Health Care
PubMed: 29220294
DOI: 10.1200/JCO.2017.74.9598 -
Surgical Oncology Clinics of North... Oct 2016There are 3 biologic groups of liposarcoma: well-differentiated and dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. In all 3... (Review)
Review
There are 3 biologic groups of liposarcoma: well-differentiated and dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. In all 3 groups, complete surgical resection is central in treatment aimed at cure and is based on grade. Radiation can reduce risk of local recurrence in high-grade lesions or minimize surgical morbidity in the myxoid/round cell liposarcoma group. The groups differ in chemosensitivity, so adjuvant chemotherapy is selectively used in histologies with metastatic potential but not in the resistant subtype dedifferentiated liposarcoma. Improved understanding of the genetic aberrations that lead to liposarcoma initiation is allowing for the rapid development of targeted therapies for liposarcoma.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Liposarcoma; Liposarcoma, Myxoid; Molecular Targeted Therapy; Multimodal Imaging; Neoplasm Grading; Neoplasm Recurrence, Local; Precision Medicine
PubMed: 27591497
DOI: 10.1016/j.soc.2016.05.007 -
World Journal of Surgery Jan 2021Esophageal lipomatous tumors, also reported as fibrovascular polyp, fibrolipoma, angiolipoma, and liposarcoma, account for less than 1% of all benign mesenchymal... (Review)
Review
BACKGROUND
Esophageal lipomatous tumors, also reported as fibrovascular polyp, fibrolipoma, angiolipoma, and liposarcoma, account for less than 1% of all benign mesenchymal submucosal tumors of the esophagus. Clinical presentation and therapy may differ based on location, size, and morphology. A comprehensive and updated systematic review of the literature is lacking.
METHODS
A systematic review of the literature was performed according to PRISMA guidelines. Pubmed, Embase, Cochrane, and Medline databases were consulted using MESH keywords. Non-English written articles and abstracts were excluded. Sex, age, symptoms at presentation, diagnosis, tumor location and size, surgical approach and technique of excision, pathology, and morphology were extracted and recorded in an electronic database.
RESULTS
Sixty-seven studies for a total of 239 patients with esophageal lipoma or liposarcoma were included in the qualitative analysis. Among 176 patients with benign lipoma, the median age was 55. The main symptoms were dysphagia (64.2%), transoral polyp regurgitation (32.4%), and globus sensation (22.7%). The majority of lipomas (85.7%) were intraluminal polyps, with a stalk originating from the upper esophagus. Overall, 165 patients underwent excision of the mass through open surgery (65.5%), endoscopy (27.9%), or laparoscopy/thoracoscopy (3.6%). Only 5 (3%) of patients required esophagectomy. Of the 11 untreated patients with an intraluminal polyp, 7 died from asphyxia. Overall, liposarcoma was diagnosed in 63 patients, and 12 (19%) underwent esophagectomy.
CONCLUSION
Esophageal lipomatous tumors are rare but potentially lethal when are intraluminal and originate from the cervical esophagus. Modern radiological imaging has improved diagnostic accuracy. Minimally invasive transoral and laparoscopic/thoracoscopic techniques represent the therapeutic approach of choice.
Topics: Esophageal Neoplasms; Esophagectomy; Humans; Lipoma; Liposarcoma
PubMed: 33026474
DOI: 10.1007/s00268-020-05789-4 -
Cellular and Molecular Life Sciences :... Oct 2016Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20 % of all adult sarcomas. Current treatment modalities (surgery, chemotherapy,... (Review)
Review
Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20 % of all adult sarcomas. Current treatment modalities (surgery, chemotherapy, and radiotherapy) all have limitations; therefore, molecularly driven studies are needed to improve the identification and increased understanding of genetic and epigenetic deregulations in LPS if we are to successfully target specific tumorigenic drivers. It can be anticipated that such biology-driven therapeutics will improve treatments by selectively deleting cancer cells while sparing normal tissues. This review will focus on several therapeutically actionable molecular markers identified in well-differentiated LPS and dedifferentiated LPS, highlighting their potential clinical applicability.
Topics: Animals; Biomarkers, Tumor; Disease Progression; Humans; Liposarcoma; MicroRNAs; Molecular Targeted Therapy
PubMed: 27173057
DOI: 10.1007/s00018-016-2266-2 -
International Journal of Molecular... May 2023Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options... (Review)
Review
Well-differentiated/de-differentiated liposarcoma (WDLPS/DDLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS); however, treatment options remain limited. WDLPS and DDLPS both exhibit the characteristic amplification of chromosome region 12q13-15, which contains the genes and . DDLPS exhibits higher amplification ratios of these two and carries additional genomic lesions, including the amplification of chromosome region 1p32 and chromosome region 6q23, which may explain the more aggressive biology of DDLPS. WDLPS does not respond to systemic chemotherapy and is primarily managed with local therapy, including multiple resections and debulking procedures whenever clinically feasible. In contrast, DDLPS can respond to chemotherapy drugs and drug combinations, including doxorubicin (or doxorubicin in combination with ifosfamide), gemcitabine (or gemcitabine in combination with docetaxel), trabectedin, eribulin, and pazopanib. However, the response rate is generally low, and the response duration is usually short. This review highlights the clinical trials with developmental therapeutics that have been completed or are ongoing, including CDK4/6 inhibitors, MDM2 inhibitors, and immune checkpoint inhibitors. This review will also discuss the current landscape in assessing biomarkers for identifying tumors sensitive to immune checkpoint inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; Liposarcoma; Immunotherapy; Docetaxel; Doxorubicin; Proto-Oncogene Proteins c-mdm2
PubMed: 37298520
DOI: 10.3390/ijms24119571 -
Oncology Research and Treatment 2022While soft-tissue sarcomas (STSs) are rare tumors, liposarcomas are among the most common type of STS and are divided into four main subtypes: atypical lipomatous... (Review)
Review
BACKGROUND
While soft-tissue sarcomas (STSs) are rare tumors, liposarcomas are among the most common type of STS and are divided into four main subtypes: atypical lipomatous tumor/well-differentiated liposarcoma; dedifferentiated liposarcoma; myxoid/round-cell liposarcoma (MLPS); and pleomorphic liposarcoma (PLPS). The four different subtypes of liposarcomas have varying underlying molecular pathology, clinical behavior, and treatment sensitivity.
SUMMARY
Surgical resection is the mainstay of treatment for patients with localized liposarcoma. Radiotherapy is often used in conjunction with surgery for improving local control of liposarcoma, with MLPS being the most radiosensitive of the four subtypes. For unresectable, advanced, or metastatic disease, the effectiveness of chemotherapy can vary by subtype, with MLPS and PLPS being considered to be chemo-sensitive; however, median survival is low at around 2 years. Current first-line treatment options for patients with liposarcoma include local treatment with or without doxorubicin, ifosfamide, or a doxorubicin-ifosfamide combination, while second-line (and beyond) treatment options include ifosfamide, gemcitabine-based combinations, trabectedin, eribulin, and possibly pazopanib as established therapies. A number of other experimental treatment options are being evaluated, including mouse double minute 2 homolog antagonists, cyclin-dependent kinase 4/6 inhibitors, immune checkpoint modulators, nuclear export inhibitors, multi-kinase inhibitors, peroxisome proliferator-activated receptor gamma agonists, or various combination regimens. This review discusses established systemic therapies and emerging experimental treatment options for the treatment of patients with liposarcoma.
KEY MESSAGE
New treatments are needed to effectively treat liposarcomas. Results from trials exploring experimental therapeutic options will further define the role that these new treatments will play in the management of the different subtypes of liposarcoma.
Topics: Doxorubicin; Humans; Ifosfamide; Liposarcoma; Sarcoma; Trabectedin
PubMed: 35609512
DOI: 10.1159/000524939 -
Cancer Treatment Reviews Jun 2020Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL),... (Review)
Review
Retroperitoneal liposarcomas are rare tumours that carry a poorer prognosis than their extremity counterparts. Within their subtypes - well differentiated (WDL), dedifferentiated (DDL), myxoid (MLS) and pleomorphic (PLS) - they exhibit a diverse genomic landscape. With recent advances in next generation sequencing, the number of studies exploring this have greatly increased. The recent literature has deepened our understanding of the hallmark MDM2/CDK4 amplification in WDL/DDL and addressed concerns about toxicity and resistance when targeting this. The FUS-DDIT3 fusion gene remains the primary focus of interest in MLS with additional potential targets described. Whole genome sequencing has driven identification of novel genes and pathways implicated in WDL/DDL outside of the classic 12q13-15 amplicon. Due to their rarity; anatomical location and histologic subtype are infrequently mentioned when reporting the results of these studies. Reports can include non-adipogenic or extremity tumours, making it difficult to draw specific retroperitoneal conclusions. This narrative review aims to provide a summary of retroperitoneal liposarcoma genomics and the implications for therapeutic targeting.
Topics: Animals; Antineoplastic Agents, Alkylating; Chromosome Aberrations; Genomics; Humans; Liposarcoma; Oncogene Proteins, Fusion; Phosphatidylinositol 3-Kinases; Retroperitoneal Neoplasms; Trabectedin
PubMed: 32278233
DOI: 10.1016/j.ctrv.2020.102013 -
Cancer Medicine Mar 2023Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options.
PURPOSE
Patients with unresectable dedifferentiated liposarcoma (DDLPS) have poor overall outcomes. Few genomic alterations have been identified with limited therapeutic options.
EXPERIMENTAL DESIGN
Patients treated at Levine Cancer Institute with DDLPS were identified. Next generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) testing were performed on tumor tissue collected at diagnosis or recurrence/progression. Confirmation of genomic alterations was performed by orthologous methods and correlated with clinical outcomes. Univariate Cox regression was used to identify genomic alterations associated with clinical outcomes.
RESULTS
Thirty-eight DDLPS patients with adequate tissue for genomic profiling and clinical data were identified. Patient characteristics included: median age at diagnosis (66 years), race (84.2% Caucasian), and median follow-up time for the entire cohort was 12.1 years with a range from approximately 3.5 months to 14.1 years. Genes involved in cell cycle regulation, including MDM2 (74%) CDK4 (65%), and CDKN2A (23%), were amplified along with WNT/Notch pathway markers: HMGA2, LGR5, MCL1, and CALR (19%-29%). While common gene mutations were identified, PDE4DIP and FOXO3 were also mutated in 47% and 34% of patients, respectively, neither of which have been previously reported. FOXO3 was associated with improved overall survival (OS) (HR 0.37; p = 0.043) along with MAML2 (HR 0.30; p = 0.040). Mutations that portended worse prognosis included RECQL4 (disease-specific survival HR 4.67; p = 0.007), MN1 (OS HR = 3.38; p = 0.013), NOTCH1 (OS HR 2.28, p = 0.086), and CNTRL (OS HR 2.42; p = 0.090).
CONCLUSIONS
This is one of the largest retrospective reports analyzing genomic aberrations in relation to clinical outcomes for patients with DDLPS. Our results suggest therapies targeting abnormalities should be explored and confirmation of prognostic markers is needed. Dedifferentiated liposarcoma is one of the most common subtypes of soft tissue sarcoma yet little is known of its molecular aberrations and possible impact on outcomes. The work presented here is an evaluation of genetic abnormalities among a population of patients with dedifferentiated liposarcoma and how they corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.
Topics: Humans; In Situ Hybridization, Fluorescence; Retrospective Studies; Prognosis; Liposarcoma; Genomics; Proto-Oncogene Proteins c-mdm2
PubMed: 36464833
DOI: 10.1002/cam4.5502 -
Modern Pathology : An Official Journal... Nov 2022Myxoid pleomorphic liposarcoma (MPLPS) is a recently described and extremely rare subtype of liposarcoma with a predilection for the mediastinum. However, the genomic...
Myxoid pleomorphic liposarcoma is distinguished from other liposarcomas by widespread loss of heterozygosity and significantly worse overall survival: a genomic and clinicopathologic study.
Myxoid pleomorphic liposarcoma (MPLPS) is a recently described and extremely rare subtype of liposarcoma with a predilection for the mediastinum. However, the genomic features of MPLPS remain poorly understood. We performed comprehensive genomic profiling of MPLPS in comparison with pleomorphic liposarcoma (PLPS) and myxoid/round cell liposarcoma (MRLPS). Of the 8 patients with MPLPS, 5 were female and 3 were male, with a median age of 32 years old (range 10-68). All except one were located in the mediastinum, with invasion of surrounding anatomic structures, including chest wall, pleura, spine, and large vessels. All cases showed an admixture of morphologies reminiscent of PLPS and MRLPS, including myxoid areas with plexiform vasculature admixed with uni- and/or multivacuolated pleomorphic lipoblasts. Less common features included well-differentiated liposarcoma-like areas, and in one case fascicular spindle cell sarcoma reminiscent of dedifferentiated LPS. Clinically, 4 experienced local recurrence, 4 had distant metastases and 5 died of disease. Compared to PLPS and MRLPS, patients with MPLPS had worse overall and progression-free survival. Recurrent TP53 mutations were present in all 8 MPLPS cases. In contrast, in PLPS, which also showed recurrent TP53 mutations (83%), RB1 and ATRX losses were more common. MRLPS was highly enriched in TERT promoter mutations (88%) and PI3K/AKT pathway mutations. Copy number profiling in MPLPS revealed multiple chromosomal gains with recurrent amplifications of chromosomes 1, 19 and 21. Importantly, allele-specific copy number analysis revealed widespread loss of heterozygosity (80% of the genome on average) in MPLPS, but not in PLPS or MRLPS. Our findings revealed genome-wide loss of heterozygosity co-existing with TP53 mutations as a characteristic genomic signature distinct from other liposarcoma subtypes, which supports the current classification of MPLPS as a stand-alone pathologic entity. These results further expand the clinicopathologic features of MPLPS, including older age, extra-mediastinal sites, and a highly aggressive outcome.
Topics: Adult; Humans; Male; Female; Child; Adolescent; Young Adult; Middle Aged; Aged; Lipopolysaccharides; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Liposarcoma; Genomics; Loss of Heterozygosity; Liposarcoma, Myxoid
PubMed: 35672466
DOI: 10.1038/s41379-022-01107-6 -
Medical Sciences (Basel, Switzerland) Nov 2023Although liposarcoma is the most prevalent soft tissue sarcoma in adults, head and neck liposarcomas are rare and account for less than 5% of all liposarcomas. The...
Although liposarcoma is the most prevalent soft tissue sarcoma in adults, head and neck liposarcomas are rare and account for less than 5% of all liposarcomas. The primary orbital location is even more exceptional, with fewer than 100 cases documented in the medical literature. Given the scarcity of cases of orbital liposarcoma and the limited familiarity of physicians and pathologists with this pathology, there is an increased risk of non-diagnosis or misdiagnosis, which may lead to inappropriate patient management. To address these challenges, we present a case of primary orbital myxoid liposarcoma and subsequently discuss the primary findings of this case based on the evidence documented in the medical literature. This comprehensive text is designed to serve as a valuable resource for healthcare professionals and pathologists, with the goal of promoting both clinical suspicion and accurate diagnosis and treatment of this rare condition in future cases.
Topics: Adult; Humans; Liposarcoma, Myxoid; Soft Tissue Neoplasms; Neck
PubMed: 37987327
DOI: 10.3390/medsci11040072