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Chua HB, Hussain RI, Shukor NA, Fam XI. Case Report: an extremely rare case of giant dedifferentiated retroperitoneal liposarcoma. Front Oncol 2025; 15:1489833. [PMID: 40165894 PMCID: PMC11955609 DOI: 10.3389/fonc.2025.1489833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 01/21/2025] [Indexed: 04/02/2025] Open
Abstract
Retroperitoneal liposarcoma, especially dedifferentiated liposarcoma (DDL), is a rare tumor type primarily affecting middle-aged and older adults in the retroperitoneum or proximal extremities. This case report highlights an exceptionally large retroperitoneal DDL that had enveloped the entire right kidney and had adhered to nearby tissues. Diagnosing retroperitoneal liposarcoma is challenging due to its asymptomatic nature until it reaches a substantial size. Imaging, particularly contrast-enhanced computed tomography (CECT), play a vital role in diagnosis, staging, and preoperative planning. Surgical resection, with the goal of R0 resection, remains the cornerstone of treatment, albeit this can be challenging due to tumor location. First-line treatment for advanced DDL involves anthracycline-based therapy. Eribulin and pazopanib show promise in second-line treatment. Ongoing clinical trials suggest a shift towards multimodal therapy. This case report reports the largest retroperitoneal liposarcoma and underscores the complexity of managing retroperitoneal DDL.
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Affiliation(s)
- Huey Bing Chua
- Urology Unit, Department of Surgery, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Rizuana Iqbal Hussain
- Department of Radiology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Nordashima Abd Shukor
- Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Xeng Inn Fam
- Urology Unit, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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Butler Z, Yu A, Honore L, Timmermann A, Demetrious M, Gitelis S, Miller I, Blank A. Characterizing the Transformation and Diagnosis of Atypical Lipomatous Tumor to Dedifferentiated Liposarcoma: Single Institutional Outcomes. J Surg Oncol 2025; 131:507-513. [PMID: 39387522 DOI: 10.1002/jso.27924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Accepted: 09/11/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION Atypical lipomatous tumor (ALT) in the extremities is a locally aggressive adipocytic tumor with the potential risk of transformation into dedifferentiated liposarcoma (DDLS). Studies seldom differentiate whether DDLS was diagnosed on initial biopsy, final resected specimen, or subsequent recurrence. Our study seeks to characterize how and when patients received their ALT or DDLS diagnoses to better understand the relationship between the two neoplasms. METHODS We performed a retrospective review of patients diagnosed with ALT or DDLS of the extremities. Clinical characteristics, including the method of diagnosis of an ALT or DDLS, time between diagnoses, and tumor recurrence was recorded. Univariate/multivariate analysis was performed to identify risk factors. RESULTS Forty-five patients were diagnosed with ALT after core needle biopsy (CNB) and 41 of them received marginal en bloc excision. Three (7.3%) of these patients had a heterogeneous tumor on final resection, pathology revealed both ALT and DDLS. Four patients (8.2%) were diagnosed with DDLS from CNB and received negative margin en bloc excision. One of these tumors was identified as heterogeneous ALT/DDLS after resection. Fifty-three patients received marginal en bloc resection without CNB after a benign lipomatous mass was suspected on CT/MRI. Among these, one (1.9%) had a tumor with a heterogeneous composition of both ALT and DDLS on pathology. There were 11 (11.7%) ALT recurrences and 1 (1.0%) DDLS recurrence after ALT resection. CONCLUSION Obtaining a proper diagnosis whether ALT or DDLS is critical. Our cohort found that amongst those concerning lipomatous lesions biopsied, 7.84% will show biopsy proven DDLS. Additionally, 6.67% of the biopsies will be false negatives and show DDLS on final pathology. Furthermore, our local recurrence for ALT was 11.7% recurring as ALT and 1.0% recurring as DDLS.
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Affiliation(s)
- Zachary Butler
- Department of Orthopedic Surgery, Division of Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Austin Yu
- Department of Orthopedic Surgery, Division of Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | | | | | - Matthew Demetrious
- Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA
| | - Steven Gitelis
- Department of Orthopedic Surgery, Division of Oncology, Rush University Medical Center, Chicago, Illinois, USA
| | - Ira Miller
- Department of Pathology, Rush University Medical Center, Chicago, Illinois, USA
| | - Alan Blank
- Department of Orthopedic Surgery, Division of Oncology, Rush University Medical Center, Chicago, Illinois, USA
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Rowe DA, Bowers WB, Mateja HL, Morgan A, Thomas D. Silent Giant: A Case of Dedifferentiated Retroperitoneal Liposarcoma Presenting as an Incidental Mesenteric Mass. Cureus 2024; 16:e72549. [PMID: 39606521 PMCID: PMC11601141 DOI: 10.7759/cureus.72549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/27/2024] [Indexed: 11/29/2024] Open
Abstract
Dedifferentiated liposarcoma (DDL) is a rare and aggressive subtype of liposarcoma, arising most commonly in the retroperitoneum but rarely presenting in the mesentery. Due to its rarity, mesenteric DDL poses significant diagnostic and therapeutic challenges, with few cases documented in the literature. Here, we report the case of a 76-year-old female admitted with acute respiratory failure secondary to pneumonia, during which an incidental finding of a large mesenteric mass was noted on computed tomography (CT) imaging. An elective exploratory laparotomy was performed one month later, revealing a large mesenteric tumor adherent to the terminal ileum, cecum, and ascending colon. En bloc resection, including right hemicolectomy and partial small bowel resection, was successfully performed. Pathology confirmed an intermediate-grade DDL. This case underscores the importance of considering mesenteric DDL in the differential diagnosis of large, asymptomatic intra-abdominal masses. Complete surgical resection remains the mainstay of treatment, with a critical focus on achieving negative margins to reduce recurrence risk. Given the aggressive nature of DDL, vigilant long-term follow-up is essential. This report contributes to the limited body of literature on mesenteric DDL and highlights the challenges in its diagnosis and management.
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Affiliation(s)
- Danielle A Rowe
- General Surgery, American University of Antigua, Osbourn, ATG
- General Surgery, Western Reserve Health Education/Northeast Ohio Medical University (NEOMED), Warren, USA
| | - William B Bowers
- General Surgery, American University of Antigua, Osbourn, ATG
- General Surgery, Western Reserve Health Education/Northeast Ohio Medical University (NEOMED), Warren, USA
| | - Heather L Mateja
- General Surgery, American University of Antigua, Osbourn, ATG
- General Surgery, Western Reserve Health Education/Northeast Ohio Medical University (NEOMED), Warren, USA
| | - Alyson Morgan
- General Surgery, Western Reserve Health Education/Northeast Ohio Medical University (NEOMED), Warren, USA
- General Surgery, Sharon Regional Medical Center, Sharon, USA
| | - David Thomas
- General Surgery, Sharon Regional Medical Center, Sharon, USA
- General Surgery, Western Reserve Health Education/Northeast Ohio Medical University (NEOMED), Warren, USA
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Seo CJ, Tan JWS, Farid M, Wong JSM, Soo KC, Chia CS, Ong CAJ. Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre. PLoS One 2024; 19:e0300594. [PMID: 38574044 PMCID: PMC10994346 DOI: 10.1371/journal.pone.0300594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 02/23/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.
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Affiliation(s)
- Chin Jin Seo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Joey Wee-Shan Tan
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
| | - Mohamad Farid
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Jolene Si Min Wong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Khee Chee Soo
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
| | - Claramae Shulyn Chia
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Chin-Ann Johnny Ong
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, Singapore, Singapore
- Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore, Singapore
- Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore
- SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- SingHealth Duke-NUS Surgery Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Research Entities, Singapore, Singapore
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Kyriazoglou A, Pagkali A, Kotsantis I, Economopoulou P, Kyrkasiadou M, Moutafi M, Gavrielatou N, Anastasiou M, Boulouta A, Pantazopoulos A, Giannakakou M, Digklia A, Psyrri A. Well-differentiated liposarcomas and dedifferentiated liposarcomas: Systemic treatment options for two sibling neoplasms. Cancer Treat Rev 2024; 125:102716. [PMID: 38492514 DOI: 10.1016/j.ctrv.2024.102716] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 03/03/2024] [Accepted: 03/05/2024] [Indexed: 03/18/2024]
Abstract
Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) account for 60 % of all liposarcomas, reflecting the heterogeneity of this type of sarcoma. Genetically, both types of liposarcomas are characterized by the amplification of MDM2 and CDK4 genes, which indicates an important molecular event with diagnostic and therapeutic relevance. In both localized WDLPS and DDLPS of the retroperitoneum and the extremities, between 25 % and 30 % of patients have local or distant recurrence, even when perioperatively treated, with clear margins present. The systemic treatment of WDLPS and DDLPS remains a challenge, with anthracyclines as the gold standard for first-line treatment. Several regimens have been tested with modest results regarding their efficacy. Herein we discuss the systemic treatment options for WDLPS and DDLPS and review their reported clinical efficacy results.
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Affiliation(s)
- A Kyriazoglou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
| | - A Pagkali
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - I Kotsantis
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - P Economopoulou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - M Kyrkasiadou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - M Moutafi
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - N Gavrielatou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - M Anastasiou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - A Boulouta
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - A Pantazopoulos
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - M Giannakakou
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
| | - A Digklia
- Sarcoma Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Lausanne, Switzerland
| | - A Psyrri
- Section of Medical Oncology, 2nd Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
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Teixeira FR, Arakaki MS, Lima HVG, Ferreira FDO, Menegozzo CAM, Silva ER, Montero EFDS, Oya T, Lima LC, Akaishi EH, Utiyama EM. Multivisceral resection for retroperitoneal liposarcoma-is it worth it? A 20-year single-center experience. Surg Today 2023; 53:1181-1187. [PMID: 37606758 DOI: 10.1007/s00595-023-02731-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 02/23/2023] [Indexed: 08/23/2023]
Abstract
PURPOSE Soft tissue sarcomas are rare malignant tumors. Liposarcoma constitutes the most frequent histological subtype of retroperitoneal sarcoma. The prognosis of soft tissue sarcomas depends on clinical and histologic characteristics. OBJECTIVE Evaluate variables that may be related to the overall and local recurrence-free survival in patients with retroperitoneal liposarcoma and discuss the need for visceral resection en-bloc for tumors. METHODS A retrospective analysis was conducted of the medical records of 60 patients seen between 1997 and 2017 who underwent surgical resection of retroperitoneal liposarcoma. RESULTS The overall survival rate at 5 years of follow-up was 75.22% (95% confidence interval [CI] 0.58-0.86). The probability of a local recurrence-free survival at 5 years of follow-up was 26.04% (95% CI 0.11-0.44). The multivariate analysis showed that dedifferentiated or pleomorphic tumors and R2/fragmented resection were associated with a shorter time to recurrence. No other characteristics markedly influenced the overall survival (P > 0.05). CONCLUSION Patients with dedifferentiated or pleomorphic tumors and incomplete resection were associated with higher local recurrence rates than others. This study reinforces the need for complete and en-bloc resection with organs when there is clear involvement or technical surgical difficulty to maintain the tumor integrity.
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Affiliation(s)
- Frederico Ribeiro Teixeira
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Mariana Sousa Arakaki
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Helber Vidal Gadelha Lima
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil.
| | - Fabio de Oliveira Ferreira
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Carlos Augusto Metidieri Menegozzo
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Eduardo Rissi Silva
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Edna Frasson de Souza Montero
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
- Laboratory of Surgical Physiopathology (LIM-62), Hospital das Clínicas (HCFMUSP), São Paulo, Brazil
| | - Toshiko Oya
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
- Nurse of Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), São Paulo, Brazil
| | - Luiz Calima Lima
- Soft Tissue Sarcoma Pathologist-Cancer Institute of the State of São Paulo (ICESP), São Paulo, Brazil
| | - Eduardo Hiroshi Akaishi
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
| | - Edivaldo Massazo Utiyama
- Divisão de Clínica Cirúrgica III - Hospital das Clínicas (HCFMUSP), Instituto Central do Hospital das Clínicas da Universidade de São Paulo, 8º andar, sala 8131, Av. Dr. Enéas de Carvalho Aguiar, 255, Cerqueira César, São Paulo, SP, 05402-000, Brazil
- Laboratory of Surgical Physiopathology (LIM-62), Hospital das Clínicas (HCFMUSP), São Paulo, Brazil
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YAMATE J. Stem cell pathology: histogenesis of malignant fibrous histiocytoma and characterization of myofibroblasts appearing in fibrotic lesions. J Vet Med Sci 2023; 85:895-906. [PMID: 37460298 PMCID: PMC10539815 DOI: 10.1292/jvms.23-0225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Accepted: 06/26/2023] [Indexed: 09/05/2023] Open
Abstract
The concept of "stem cell pathology" is to establish the role of the stem cells by exploring their contribution to lesion development. The somatic stem cells are present in the body. Malignant fibrous histiocytoma (MFH; recently named "undifferentiated pleomorphic sarcoma") includes pluripotential undifferentiated mesenchymal stem cells as a cell element. An antibody (A3) generated by using rat MFH cells as the antigen labels somatic stem cells such as bone marrow stem cells and immature endothelial cells and pericytes, as well as immature epithelial cells in epithelialization. By using A3 and other antibodies recognizing somatic stem cells, it is considered that myofibroblasts appearing in rat fibrotic lesions are developed partly from immature hepatic stellate cells in hepatic fibrosis, immature pancreatic stellate cells in pancreatic fibrosis, pericytes/endothelial cells in neovascularization in injured tissues, as well as via the epithelial-mesenchymal transition. These progenitors may be in the stem cell lineage. In this review, the author introduces the histogenesis of MFH and the characteristics of myofibroblasts appearing in fibrosis, based mainly on the author's studies.
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Affiliation(s)
- Jyoji YAMATE
- Laboratory of Veterinary Pathology, Osaka Metropolitan University, Osaka, Japan
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8
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Zhou MY, Bui NQ, Charville GW, Ganjoo KN, Pan M. Treatment of De-Differentiated Liposarcoma in the Era of Immunotherapy. Int J Mol Sci 2023; 24:ijms24119571. [PMID: 37298520 DOI: 10.3390/ijms24119571] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 05/30/2023] [Accepted: 05/30/2023] [Indexed: 06/12/2023] Open
Abstract
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 CDK4 and MDM2. 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.
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Affiliation(s)
- Maggie Y Zhou
- Sarcoma Program, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
| | - Nam Q Bui
- Sarcoma Program, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
| | - Gregory W Charville
- Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA
| | - Kristen N Ganjoo
- Sarcoma Program, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
| | - Minggui Pan
- Sarcoma Program, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94304, USA
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9
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A case of dedifferentiated liposarcoma of the descending colon. Clin J Gastroenterol 2023; 16:361-365. [PMID: 36735203 DOI: 10.1007/s12328-023-01762-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/17/2023] [Indexed: 02/04/2023]
Abstract
A 54-year-old man referred to our hospital for abdominal distension. He had no medical history. On physical examination, he complained lower abdominal distention, and had no spontaneous pain or tenderness. The blood tests showed that CEA and CA19-9 levels were within normal limits. Colonoscopy revealed a submucosal tumor with irregularities and mucosal defects in the descending colon. Computed tomography (CT) showed a 3-cm-diameter mass in the descending colon and ascites. Due to the presence of ascites, laparoscopic examination was performed, which revealed multiple peritoneal seeding of the tumor. Given the presence of peritoneal dissemination, the tumor was determined to be unresectable, and a histological examination was performed from the disseminated nodule. Pathologically, atypical spindle cells were observed and infiltrated into adipose tissue. Additional immunohistochemistry revealed positive expression for Murine double minute 2 (MDM2) and Cyclin-dependent kinase 4 (CDK4), and fluorescence in situ hybridization showed amplification of MDM2. Thus, the tumor was diagnosed with a dedifferentiated liposarcoma of the descending colon. Liposarcoma is a type of soft-tissue sarcoma that arises from soft tissues such as the extremities or retroperitoneum. Here, we report an extremely rare case of a dedifferentiated liposarcoma of the colon.
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10
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Morii T, Anazawa U, Sato C, Iwata S, Nakagawa M, Endo M, Nakamura T, Ikuta K, Nishida Y, Nakayama R, Udaka T, Kawamoto T, Kito M, Sato K, Imanishi J, Akiyama T, Kobayashi H, Nagano A, Outani H, Toki S, Nishisho T, Sasa K, Suehara Y, Kawano H, Ueda T, Morioka H. Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG). EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:353-361. [PMID: 36088237 DOI: 10.1016/j.ejso.2022.08.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 08/15/2022] [Accepted: 08/22/2022] [Indexed: 11/26/2022]
Abstract
BACKGROUND Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.
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Affiliation(s)
- Takeshi Morii
- Department of Orthopaedic Surgery, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
| | - Ukei Anazawa
- Department of Orthopaedic Surgery, Tokyo Dental College Ichikawa General Hospital, 5-11-13, Sugano, Ichikawa, Chiba, 272-8513, Japan
| | - Chiaki Sato
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Shintaro Iwata
- Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Makoto Nakagawa
- Department of Orthopaedic Surgery, Kyushu University School of Medicine, 3-1-1 Maidashi, Hagashi-ku, Fukuoka, Fukuoka, 812-8582, Japan
| | - Makoto Endo
- Department of Orthopaedic Surgery, Kyushu University School of Medicine, 3-1-1 Maidashi, Hagashi-ku, Fukuoka, Fukuoka, 812-8582, Japan
| | - Tomoki Nakamura
- Department of Orthopedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan
| | - Kunihiro Ikuta
- Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Yoshihiro Nishida
- Department of Orthopaedic Surgery, Nagoya University Graduate School and School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan
| | - Robert Nakayama
- Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Toru Udaka
- Department of Orthopaedic Surgery, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Teruya Kawamoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Munehisa Kito
- Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Kenji Sato
- Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo, 173-8606, Japan
| | - Jungo Imanishi
- Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo, 173-8606, Japan
| | - Toru Akiyama
- Departments of Orthopaedic Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama, Saitama, 330-8503, Japan
| | - Hiroshi Kobayashi
- Department of Orthopaedic Surgery, The University of Tokyo Faculty of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Akihito Nagano
- Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, Gifu, 501-1194, Japan
| | - Hidetatsu Outani
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shunichi Toki
- Department of Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, Tokushima, 770-8503, Japan
| | - Toshihiko Nishisho
- Department of Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima, Tokushima, 770-8503, Japan
| | - Keita Sasa
- Department of Orthopaedic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Yoshiyuki Suehara
- Department of Orthopaedic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
| | - Hirotaka Kawano
- Department of Orthopaedic Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo, 173-8606, Japan
| | - Takafumi Ueda
- Department of Orthopaedic Surgery, National Hospital Organization Osaka National Hospital, 2-1-14 Houenzaka, Chuo-ku, Osaka, Osaka, 540-0006, Japan
| | - Hideo Morioka
- Department of Orthopaedic Surgery, National Hospital Organization Tokyo Medical Center, 2-5-1, Higashigaoka, Meguro-ku, Tokyo, 152-8902, Japan
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11
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Park N, Kuk JC, Shin EJ, Lim DR. Surgery of intraabdominal giant dedifferentiated liposarcoma of ascending colon mesentery: A rare case report. Int J Surg Case Rep 2022; 98:107482. [PMID: 35973321 PMCID: PMC9400074 DOI: 10.1016/j.ijscr.2022.107482] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 08/02/2022] [Accepted: 08/07/2022] [Indexed: 11/29/2022] Open
Abstract
Introduction Liposarcoma, a lipogenic tumor of large deep-seated connective tissue space, presents the most common type of soft tissue sarcoma arising in the retroperitoneum. Liposarcoma that arises from colonic mesentery is especially a very rare disease. The present case describes a surgery of giant dedifferentiated liposarcoma at ascending colon mesentery. Presentation of case A 47-year-old South Korean man was admitted and presented with palpable abdominal mass. Abdominal pelvic computed tomography scan revealed a huge mass at his right sided abdomen (about 25 × 19 cm sized mass at right abdomen with encapsulation). After the surgery, the entire mass was completely excised en bloc with the ascending colon. The specimen consisted of multinodular, pinkish tanned, focally myxoid tissue, which measured up to 25.5 × 19 × 12.5 cm. Final pathological analysis reported dedifferentiated liposarcoma (high grade sarcoma) with MDM2 and CDK2 (+) in immunohistochemistry. Conclusion The present case report concerns a 47-year-old male with giant dedifferentiated liposarcoma arising from colonic mesentery and achieved en-bloc resection of liposarcoma with right hemicolectomy.
Dedifferentiated liposarcoma arising from colonic mesentery is a rare form of the soft tissue sarcoma. In giant dedifferentiated liposarcoma, grossly complete resection is known as the better prognostic factor. liposarcoma excision with right hemicolectomy was inevitable for this case to achieve the complete resection due to colon wall invasion.
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Affiliation(s)
- Nahyeon Park
- Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Jung Cheol Kuk
- Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Eung Jin Shin
- Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Dae Ro Lim
- Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
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12
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Li Y, Wu G, Zhang Y, Yang W, Wang X, Duan L, Niu L, Chen J, Zhou W, Liu J, Fan D, Hong L. Effects of marital status on survival of retroperitoneal liposarcomas stratified by age and sex: A population-based study. Cancer Med 2022; 12:1779-1790. [PMID: 35758717 PMCID: PMC9883417 DOI: 10.1002/cam4.4962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Previous studies have shown that marital status is associated with survival in patients with a variety of cancer types, including lung cancer, prostate cancer, and bladder cancer. However, to date, the impact of marital status on the survival of patients with retroperitoneal liposarcomas (RPLs) has not been established. METHODS A total of 1211 eligible patients diagnosed with RPLs were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The relationships between marital status and survival in patients with RPLs were assessed. Patients were stratified by age to determine whether an association exists between marital status and age. We also probed the association between marital status and survival in males and females. RESULTS Our findings suggest that divorced, separated, or widowed patients have more advanced cancer stages, and more of these patients do not undergo surgery. Meanwhile, divorced, separated, or widowed patients have worse survival outcomes than married patients (overall survival (OS): HR = 1.66 (95% CI, 1.12, 2.46)); cancer-specific survival (CSS): HR = 1.90 (95% CI, 1.13, 3.19)). OS does not differ between single patients and married patients (HR = 1.21 [95% CI, 0.81, 1.81]) or CSS (HR = 1.36 [95% CI, 0.80, 2.29]). In addition, these results demonstrate that being divorced, separated, or widowed can play a significant detrimental role in mortality in older and female patients. CONCLUSION Married patients have earlier disease stages at diagnosis and better survival outcomes than divorced, separated, or widowed patients with RPLs. In addition, this effect is especially pronounced in older people and females.
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Affiliation(s)
- Yiding Li
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Guiling Wu
- School of Aerospace MedicineFourth Military Medical UniversityXi'anChina
| | - Yujie Zhang
- Department of Histology and Embryology, School of Basic MedicineXi'an Medical UniversityXi'anChina
| | - Wanli Yang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Xiaoqian Wang
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Lili Duan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Liaoran Niu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Junfeng Chen
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Wei Zhou
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Jinqiang Liu
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Daiming Fan
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
| | - Liu Hong
- State Key Laboratory of Cancer Biology and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anChina
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13
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Thway K. What’s new in adipocytic neoplasia? Histopathology 2021; 80:76-97. [DOI: 10.1111/his.14548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 08/18/2021] [Accepted: 08/20/2021] [Indexed: 12/22/2022]
Affiliation(s)
- Khin Thway
- Sarcoma Unit Royal Marsden Hospital London UK
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14
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Thway K, Fisher C. Undifferentiated and dedifferentiated soft tissue neoplasms: Immunohistochemical surrogates for differential diagnosis. Semin Diagn Pathol 2021; 38:170-186. [PMID: 34602314 DOI: 10.1053/j.semdp.2021.09.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 09/14/2021] [Accepted: 09/27/2021] [Indexed: 12/23/2022]
Abstract
Undifferentiated soft tissue sarcomas (USTS) are described in the current World Health Organization Classification of Soft Tissue and Bone Tumours as those showing no identifiable line of differentiation when analyzed by presently available technologies. This is a markedly heterogeneous group, and the diagnosis of USTS remains one of exclusion. USTS can be divided into four morphologic subgroups: pleomorphic, spindle cell, round cell and epithelioid undifferentiated sarcomas, with this combined group accounting for up to 20% of all soft tissue sarcomas. As molecular advances enable the stratification of emerging genetic subsets within USTS, particularly within undifferentiated round cell sarcomas, other groups, particularly the category of undifferentiated pleomorphic sarcomas (UPS), still remain difficult to substratify and represent heterogeneous collections of neoplasms often representing the common morphologic endpoints of a variety of malignant tumors of various (mesenchymal and non-mesenchymal) lineages. However, recent molecular developments have also enabled the identification and correct classification of many tumors from various lines of differentiation that would previously have been bracketed under 'UPS'. This includes pleomorphic neoplasms and dedifferentiated neoplasms (the latter typically manifesting with an undifferentiated pleomorphic morphology) of mesenchymal (e.g. solitary fibrous tumor and gastrointestinal stromal tumor) and non-mesenchymal (e.g. melanoma and carcinoma) origin. The precise categorization of 'pleomorphic' or 'undifferentiated' neoplasms is critical for prognostication, as, for example, dedifferentiated liposarcoma typically behaves less aggressively than other pleomorphic sarcomas, and for management, including the potential for targeted therapies based on underlying recurrent molecular features. In this review we focus on undifferentiated and dedifferentiated pleomorphic and spindle cell neoplasms, summarizing their key genetic, morphologic and immunophenotypic features in the routine diagnostic setting, and the use of immunohistochemistry in their principal differential diagnosis, and highlight new developments and entities in the group of undifferentiated and dedifferentiated soft tissue sarcomas.
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Affiliation(s)
- Khin Thway
- Sarcoma Unit, Royal Marsden Hospital, London, SW3 6JJ, United Kingdom; Division of Molecular Pathology, The Institute of Cancer Research, 237 Fulham Rd, London, SW3 6JB, United Kingdom.
| | - Cyril Fisher
- Division of Molecular Pathology, The Institute of Cancer Research, 237 Fulham Rd, London, SW3 6JB, United Kingdom; Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
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15
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Liu Q, Bao Q, Xu Y, Fu Y, Jin Z, Wang J, Zhang W, Shen Y. MCM4 Is a Novel Biomarker Associated With Genomic Instability, BRCAness Phenotype, and Therapeutic Potentials in Soft-Tissue Sarcoma. Front Cell Dev Biol 2021; 9:666376. [PMID: 34178990 PMCID: PMC8222794 DOI: 10.3389/fcell.2021.666376] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 05/11/2021] [Indexed: 02/02/2023] Open
Abstract
Soft-tissue sarcoma (STS) is represented by a heterogeneous group of rare malignancies with various molecular oncogenesis. Therapies targeting DNA repair pathways in STS have achieved minimal progress, potentially due to the lack of molecular biomarker(s) beyond the histology subtype. In this report, we comprehensively analyzed the expression profiles of 100 liposarcomas (LPSs), the most common STS subtype, in comparison with 21 adipose tissues from multiple GEO datasets to identify the potential prognostic and therapeutic biomarker for LPS. Furthermore, we investigated TCGA database, our archived tumor samples, and patient-derived tumor cell cultures (PTCCs) as a validation. We identified a total of 69 common differentially expressed genes (DEGs) among public datasets, with mini-chromosome maintenance protein 4 (MCM4) identified as a novel biomarker correlated with patients’ clinical staging and survival outcome. MCM4-high expression LPS was characterized by MCM4 copy number increase, genomic instability, and BRCAness phenotype compared with the MCM4-low expression counterpart. In contrast, the mutational and the immune landscape were minimally different between the two groups. Interestingly, the association of MCM4-high expression with genomic instability and BRCAness were not only validated in LPS samples from our institution (n = 66) but also could be expanded to the pan-sarcoma cohort from TCGA database (n = 263). Surprisingly, based on four sarcoma cell lines and eight PTCCs (three LPS and five other sarcoma), we demonstrated that MCM4 overexpression tumors were therapeutically sensitive to PARP inhibitor (PARPi) and platinum chemotherapy, independent of the histology subtypes. Our study, for the first time, suggested that MCM4 might be a novel prognostic biomarker, associated with dysregulated DNA repair pathways and potential therapeutic vulnerability in STS.
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Affiliation(s)
- Qi Liu
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiyuan Bao
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yiqi Xu
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yucheng Fu
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhijian Jin
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Wang
- Shanghai Institute of Orthopedics and Traumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weibin Zhang
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Institute of Orthopedics and Traumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhui Shen
- Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Institute of Orthopedics and Traumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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16
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Chen J, Hang Y, Gao Q, Huang X. Surgical Diagnosis and Treatment of Primary Retroperitoneal Liposarcoma. Front Surg 2021; 8:672669. [PMID: 34150840 PMCID: PMC8211986 DOI: 10.3389/fsurg.2021.672669] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 05/10/2021] [Indexed: 12/30/2022] Open
Abstract
Background: Primary retroperitoneal liposarcoma (PRPLS) is the most common soft tissue sarcoma of the retroperitoneum with high recurrence rate and short overall survival (OS). Methods: A retrospective review of 51 patients with PRPLS, treated between September 1, 2009 and November 30, 2020, was conducted to evaluate clinical outcomes of PRPLS resection. Patient demographics, histopathologic subtypes, overall survival (OS), progression-free survival (PFS), disease recurrence rate, and tumor stage were reviewed and analyzed. Univariate analysis was done to identify factors potentially affecting OS and PFS of PRPLS patients. Multivariate Cox proportional hazards analysis was used to evaluate the impact of various clinicopathological factors on OS and PFS of PRPLS patients. Results: Fifty-one PRPLS patients (28 Males, 23 Females; mean age 56.25 years) were evaluated. There was no significant effect of age, gender, contiguous organ resection, degree of differentiation and tumor size on the OS and PFS of the patients. Univariate analysis showed that negative surgical margin and early tumor stage significantly correlated with OS and PFS (all P < 0.001). Multivariate analysis showed that tumor stage [hazard ratio (HR) = 1.177, P = 0.001] was an independent predictors of poor progression-free survival, and surgical margins [HR = 4.0674 P = 0.038] and tumor stage [HR = 1.167 P = 0.001] were identified as independent predictors of poor overall survival. Conclusion: Negative surgical margin is a prognostic factor of OS, and can prolong the postoperative survival time of PRPLS patients. Tumor stage is a prognostic factor for OS and PFS, and can influence the survival of PRPLS patients. Earlier tumor stages of PRPLS are associated with significantly better outcomes.
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Affiliation(s)
- Jie Chen
- Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Ying Hang
- Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Qi Gao
- Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xinyu Huang
- Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
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17
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Fernández Hernández JÁ, Navarro-Barrios Á, Gil Vázquez PJ, Gil JE, Varona Garcíal L, López Motos D, Fernández Selles C, Nieto G, Frutos Bernal MD, Torres Salmerón G, Soria Cogollos T. [Giant lipomas or retroperitoneal liposarcomas? Controversies in their diagnosis and treatment]. REVISTA ESPAÑOLA DE PATOLOGÍA : PUBLICACIÓN OFICIAL DE LA SOCIEDAD ESPAÑOLA DE ANATOMÍA PATOLÓGICA Y DE LA SOCIEDAD ESPAÑOLA DE CITOLOGÍA 2021; 54:75-84. [PMID: 33726894 DOI: 10.1016/j.patol.2020.06.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 05/19/2020] [Accepted: 06/09/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Retroperitoneal lipomas are extremely rare tumors that must be differentiated from well-differentiated liposarcomas (WD-LPS). OBJECTIVES To summarize the evidence about giant retroperitoneal lipomas or liposarcomas; and to elaborate recommendations for their management. DATA SOURCES A systematic literature search from January 1985 to December 2019 and a review of our own cases was performed. RESULTS Our series comprises four patients, two females and two males. The diagnosis was incidental in two cases. The medium size was 26 cm, being two cases located exclusively in the retroperitoneum, one in the inguinal region and one in the buttock via pelvic space. All cases were surgically removed being confirmed the initial diagnosis of retroperitoneal lipomas in two cases, as the rest two cases were classified as WD_LPS after MDM2/CDK4 genetic analysis. The review of the available literature plus our own cases revealed 30 cases, of which 58% were woman. Only two cases were asymptomatic. The main symptom was abdominal mass (53%) followed by abdominal pain (40,6%). The median size of the lesions was 24,9 cm with a median weight of 4.576,3 g. All cases were surgically removed, being necessary to remove contiguous organs in only four cases (12,5%). CONCLUSIONS Retroperitoneal lipoma is a rare tumor which must be differentiated from WD-LPS. This is a very difficult task, being necessary to determinate MDM2 status (by FISH or MLPA), present in liposarcoma but not in lipomas, for its correct diagnosis. The treatment must be based on a complete surgical resection with negative margins.
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Affiliation(s)
| | - Álvaro Navarro-Barrios
- Cirugía General y Aparato Digestivo. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España.
| | - Pedro José Gil Vázquez
- Cirugía General y Aparato Digestivo. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
| | - José Emilio Gil
- Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
| | - Laura Varona Garcíal
- Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
| | - David López Motos
- Servicio de Anatomía Patológica. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
| | - Carlos Fernández Selles
- Servicio de Anatomía Patológica. Hospital Clínico Universitario de Valencia, Valencia, España
| | - Gemma Nieto
- Servicio de Anatomía Patológica. Hospital Clínico Universitario de Valencia, Valencia, España
| | | | - Gloria Torres Salmerón
- Cirugía General y Aparato Digestivo. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
| | - Teresa Soria Cogollos
- Cirugía General y Aparato Digestivo. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, España
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18
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Casadei L, Choudhury A, Sarchet P, Mohana Sundaram P, Lopez G, Braggio D, Balakirsky G, Pollock R, Prakash S. Cross-flow microfiltration for isolation, selective capture and release of liposarcoma extracellular vesicles. J Extracell Vesicles 2021; 10:e12062. [PMID: 33643547 PMCID: PMC7887429 DOI: 10.1002/jev2.12062] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 12/20/2020] [Accepted: 01/12/2021] [Indexed: 12/23/2022] Open
Abstract
We present a resource‐efficient approach to fabricate and operate a micro‐nanofluidic device that uses cross‐flow filtration to isolate and capture liposarcoma derived extracellular vesicles (EVs). The isolated extracellular vesicles were captured using EV‐specific protein markers to obtain vesicle enriched media, which was then eluted for further analysis. Therefore, the micro‐nanofluidic device integrates the unit operations of size‐based separation with CD63 antibody immunoaffinity‐based capture of extracellular vesicles in the same device to evaluate EV‐cargo content for liposarcoma. The eluted media collected showed ∼76% extracellular vesicle recovery from the liposarcoma cell conditioned media and ∼32% extracellular vesicle recovery from dedifferentiated liposarcoma patient serum when compared against state‐of‐art extracellular vesicle isolation and subsequent quantification by ultracentrifugation. The results reported here also show a five‐fold increase in amount of critical liposarcoma‐relevant extracellular vesicle cargo obtained in 30 min presenting a significant advance over existing state‐of‐art.
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Affiliation(s)
- Lucia Casadei
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA
| | - Adarsh Choudhury
- Department of Mechanical and Aerospace Engineering The Ohio State University Columbus Ohio USA
| | - Patricia Sarchet
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA
| | | | - Gonzalo Lopez
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA
| | - Danielle Braggio
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA
| | - Gita Balakirsky
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA
| | - Raphael Pollock
- Department of Mechanical and Aerospace Engineering The Ohio State University Columbus Ohio USA
| | - Shaurya Prakash
- Comprehensive Cancer Center The Ohio State University Columbus Ohio USA.,Department of Mechanical and Aerospace Engineering The Ohio State University Columbus Ohio USA
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Rioja P, Valencia G, Centurión-Rodriguez C, Morante Z, Bravo M, Huanca L, Morante C. Renal liposarcoma: case report and review of systemic treatment. Ecancermedicalscience 2021; 15:1173. [PMID: 33680087 PMCID: PMC7929774 DOI: 10.3332/ecancer.2021.1173] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Indexed: 11/06/2022] Open
Abstract
Liposarcomas are malignant mesenchymal tumours usually located in the retroperitoneum, rarely occurring as a single lesion in the kidney. We present a case of a 59-year-old male patient with a left renal mass detected by computed tomography scan. He underwent radical nephrectomy and the histopathological study reported a primary undifferentiated liposarcoma of the kidney without nodal involvement. After 15 months of surgery, he remained asymptomatic and without evidence of disease recurrence. The objective of this report is to present a case and literature review with current evidence of treatment options and prognostic factors for survival.
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Affiliation(s)
- Patricia Rioja
- Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
| | - Guillermo Valencia
- Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
| | | | - Zaida Morante
- Medical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
| | - Mercedes Bravo
- Pathology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
| | - Lourdes Huanca
- Pathology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
| | - Carlos Morante
- Surgical Oncology Department, Instituto Nacional de Enfermedades Neoplásicas, Lima 15038, Peru
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20
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Tucci JJ, Dashti NK, Cates JMM. A Proposed Staging System for Improved Prognostication of MDM2-amplified Liposarcoma. Am J Surg Pathol 2021; 45:101-107. [PMID: 32796171 DOI: 10.1097/pas.0000000000001554] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Despite the release of anatomic site-specific staging systems for soft tissue sarcomas in the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, the algorithms for sarcomas arising in the extremities/trunk and retroperitoneum differ only in the staging of lymph node metastasis. The retroperitoneum not only provides a larger potential space for tumor growth before the clinical presentation, but its anatomic complexities complicate surgical resection and adversely affect disease-free survival. Here, we propose a new staging system for MDM2-amplified liposarcomas (well-differentiated and dedifferentiated subtypes) that properly emphasizes retroperitoneal localization, degree of differentiation (histologic subtype), and presence of distant metastasis. A retrospective cohort of 4146 adult patients with surgically resected liposarcoma was extracted from the SEER database to compare the natural history of MDM2-amplified liposarcomas arising in the extremities/trunk or retroperitoneum. Separate training and validation datasets were created, and Cox proportional hazard regression, multivariable nonlinear regression, and nomographic analyses determined the most significant parameters in predicting sarcoma-specific death. A new staging system was derived and its predictive accuracy was compared with the AJCC, eighth edition system using areas under receiver operating characteristic curves and multiple concordance indices. Multivariable analysis showed that dedifferentiation (hazard ratio [HR]=3.7±0.5; P<0.0005), retroperitoneal location (HR=3.2±0.5; P<0.0005), and distant metastasis (HR=2.4±0.6; P=0.002), but not categorized tumor size (pT category), had the largest effects on sarcoma-specific survival. A new staging system based on these predictive factors demonstrated better discrimination between tumor stages, higher concordance with clinical outcomes, and greater predictive accuracy than the AJCC eighth edition staging system (86±1% vs. 83±2%; P=0.005). Statistical analysis of a large national cohort failed to confirm that categorized tumor size is a useful criterion by which to stage MDM2-amplified liposarcoma. A simplified staging system based on anatomic location and dedifferentiation outperforms the current AJCC staging system. Anatomic localization and histologic grade, and not tumor size, should be included in any future liposarcoma-specific staging system.
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Affiliation(s)
- Jonathan J Tucci
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
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21
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Sbaraglia M, Bellan E, Dei Tos AP. The 2020 WHO Classification of Soft Tissue Tumours: news and perspectives. Pathologica 2020; 113:70-84. [PMID: 33179614 PMCID: PMC8167394 DOI: 10.32074/1591-951x-213] [Citation(s) in RCA: 523] [Impact Index Per Article: 104.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 10/19/2020] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal tumours represent one of the most challenging field of diagnostic pathology and refinement of classification schemes plays a key role in improving the quality of pathologic diagnosis and, as a consequence, of therapeutic options. The recent publication of the new WHO classification of Soft Tissue Tumours and Bone represents a major step toward improved standardization of diagnosis. Importantly, the 2020 WHO classification has been opened to expert clinicians that have further contributed to underline the key value of pathologic diagnosis as a rationale for proper treatment. Several relevant advances have been introduced. In the attempt to improve the prediction of clinical behaviour of solitary fibrous tumour, a risk assessment scheme has been implemented. NTRK-rearranged soft tissue tumours are now listed as an "emerging entity" also in consideration of the recent therapeutic developments in terms of NTRK inhibition. This decision has been source of a passionate debate regarding the definition of "tumour entity" as well as the consequences of a "pathology agnostic" approach to precision oncology. In consideration of their distinct clinicopathologic features, undifferentiated round cell sarcomas are now kept separate from Ewing sarcoma and subclassified, according to the underlying gene rearrangements, into three main subgroups (CIC, BCLR and not ETS fused sarcomas) Importantly, In order to avoid potential confusion, tumour entities such as gastrointestinal stroma tumours are addressed homogenously across the different WHO fascicles. Pathologic diagnosis represents the integration of morphologic, immunohistochemical and molecular characteristics and is a key element of clinical decision making. The WHO classification is as a key instrument to promote multidisciplinarity, stimulating pathologists, geneticists and clinicians to join efforts aimed to translate novel pathologic findings into more effective treatments.
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Affiliation(s)
- Marta Sbaraglia
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - Elena Bellan
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy
| | - Angelo P Dei Tos
- Department of Pathology, Azienda Ospedale Università Padova, Padova, Italy.,Department of Medicine, University of Padua School of Medicine, Padua, Italy
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22
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Volkov AY, Kozlov NA, Nered SN, Stilidi IS, Stroganova AM, Arkhiri PP, Antonova EY, Privezentsev SA. [Retroperitoneal dedifferentiated liposarcomas: semi-quantitative assessment of the dedifferentiated component and prognosis]. Arkh Patol 2020; 82:25-32. [PMID: 33054029 DOI: 10.17116/patol20208205125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To evaluate the impact of malignancy grade and the proportion of the dedifferentiated component (DC) in retroperitoneal dedifferentiated liposarcomas (DDLS) on the course and prognosis of the disease. MATERIAL AND METHODS The retrospective study enrolled 74 patients with primary retroperitoneal DDLS who underwent radical surgical treatment in the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia. Histological surgery specimens from all cases of DDLS were reexamined and reclassified. According to malignancy grades and the proportion of the dedifferentiated component in the tumor, the patients were divided into the comparison groups included in the intergroup analysis of overall and relapse-free survival (OS and RFS) rates. The authors also analyzed the relationship between the proportion of the dedifferentiated component in DDLS and the frequency of adjacent organ invasion. RESULTS Patients with a more than 15% dedifferentiated component had significantly lower OS rates than those with a less than 15% one (p=0.0001; log-rank test). The median OS in the DDLS group with a less than 15% dedifferentiated component was 91 months (95% CI, 82-100); that in the DDLS group with a more than 15% dedifferentiated component was 29 months (95% CI 17-41). The 5-year overall survival rates in the groups with less than 15% and more than 15% dedifferentiated components were 69% and 2%, respectively. The group with a more than 15% dedifferentiated component had significantly lower RFS rates than that with a less than 15% one (p=0.0001; log-rank test). In the DDLS groups with less than 15% and more than 15% dedifferentiated components, the median RFS rates were 25 months (95% CI 23-27) and 13 months (95% CI 8-18), respectively. In these groups, the 2-year RFS rates were equal to 50% and 9%, respectively. In the DDLS groups with less than 15% and more than 15% dedifferentiated components, pathologically confirmed invasion into the adjacent organs was observed in 32% and 63% of cases, respectively. There were no statistically significant differences in the OS and RFS of patients with DDLS according to tumor grade (p=0.069; p=0.102). CONCLUSION This investigation suggests that DDLS have a more aggressive course with an increasing proportion of the dedifferentiated component in the tumor. Considering the histological variability in the dedifferentiated component, which is demonstrated in the research and scientific literature, as well as lack of a prognostic impact of histological grade, the authors believe that semi-quantitative assessment of the proportion of the dedifferentiated component in DDLS is able to serve as a simple and efficient morphological marker for the course of the disease and prognosis in retroperitoneal DDLS.
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Affiliation(s)
- A Yu Volkov
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - N A Kozlov
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - S N Nered
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - I S Stilidi
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - A M Stroganova
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - P P Arkhiri
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
| | - E Yu Antonova
- Blokhin National Medical Research Center of Oncology, Moscow, Russia
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Patt A, Demoret B, Stets C, Bill KL, Smith P, Vijay A, Patterson A, Hays J, Hoang M, Chen JL, Mathé EA. MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models. Cancers (Basel) 2020; 12:cancers12082157. [PMID: 32759684 PMCID: PMC7463633 DOI: 10.3390/cancers12082157] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/22/2020] [Accepted: 07/30/2020] [Indexed: 01/01/2023] Open
Abstract
Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 17 differentially abundant metabolites across both panels (FDR < 0.05, log2 fold change < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome.
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Affiliation(s)
- Andrew Patt
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA;
- Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, 9800 Medical Center Dr., Rockville, MD 20892, USA
- Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA
| | - Bryce Demoret
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
| | - Colin Stets
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
| | - Kate-Lynn Bill
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
| | - Philip Smith
- The Huck Institutes of Life Sciences, Penn State University, State College, PA 16802, USA; (P.S.); (A.V.); (A.P.)
| | - Anitha Vijay
- The Huck Institutes of Life Sciences, Penn State University, State College, PA 16802, USA; (P.S.); (A.V.); (A.P.)
| | - Andrew Patterson
- The Huck Institutes of Life Sciences, Penn State University, State College, PA 16802, USA; (P.S.); (A.V.); (A.P.)
| | - John Hays
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
| | - Mindy Hoang
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
| | - James L. Chen
- Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA; (B.D.); (C.S.); (K.-L.B.); (J.H.); (M.H.)
- Correspondence: (J.L.C.); (E.A.M.)
| | - Ewy A. Mathé
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA;
- Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, 9800 Medical Center Dr., Rockville, MD 20892, USA
- Correspondence: (J.L.C.); (E.A.M.)
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What Is the Role of Neoadjuvant Radiation Therapy for Retroperitoneal Sarcoma? Adv Surg 2020; 54:273-284. [PMID: 32713436 DOI: 10.1016/j.yasu.2020.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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25
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Lam-Chung CE, Rodríguez-Orihuela DL, Arízaga-Ramírez R, Almeda-Valdés P, Castillo-Valdez AK, Magaña-Pérez K, Ventura-Gallegos JL, Gamboa-Domínguez A, De Anda González J, Gómez-Pérez FJ, Cuevas-Ramos D. ACROMEGALY AND A GIANT RETROPERITONEAL LIPOSARCOMA PRODUCING IGF-1. AACE Clin Case Rep 2020; 6:e165-e169. [PMID: 32671218 DOI: 10.4158/accr-2020-0061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 03/03/2020] [Indexed: 11/15/2022] Open
Abstract
Objective Liposarcoma is the most common histotype of retroperitoneal sarcomas, representing up to 45% of all cases. We report a rare combination of acromegaly and liposarcoma in the same individual. Methods Laboratory and imaging studies including an oral glucose tolerance test, measurements of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), and a computed tomography scan were performed. Results The patient was a 60-year-old male with a history of acromegaly diagnosed on the basis of elevated IGF-1 at 1,373 ng/mL (age-appropriate reference range is 87 to 225 ng/mL) and macroadenoma treated with transsphenoidal surgery. He presented 8 years later with a history of abdominal distension and weight loss. Physical examination was notable for a right-sided abdominal mass that was tense and non-fluctuant. Two years earlier, he had a post oral glucose tolerance test GH level <0.25 ng/mL and IGF-1 level of 256 ng/mL (age-appropriate reference range is 55 to 206 ng/mL). Pituitary magnetic resonance imaging reported a 3.7 × 2.0-mm left-sided parasagittal lesion. Computed tomography scan showed a 25.0 × 22.0 × 32.3-cm heterogeneous giant mass in the right abdomen corresponding to a liposarcoma causing displacement of kidney, liver, and bowel loops. The patient was treated with a complete en bloc resection of the liposarcoma with the right kidney (45 × 33 × 17 cm) and tumor (9,400 g). Immunohistochemical examination revealed positive IGF-1 and GH staining. The patient suffered postoperative gastrointestinal bleeding that resulted in hemorrhagic shock and died on the 29th postoperative day after a cardiorespiratory arrest. Conclusion Acromegalic patients are at increased risk of developing various types of neoplasms. This is the first documented coexistence of liposarcoma and history of acromegaly.
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26
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Homsy P, Heiskanen I, Sampo M, Rönty M, Tukiainen E, Blomqvist C. Single centre 30-year experience in treating retroperitoneal liposarcomas. J Surg Oncol 2020; 122:1163-1172. [PMID: 32668067 DOI: 10.1002/jso.26118] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 07/04/2020] [Indexed: 11/10/2022]
Abstract
BACKGROUND AND OBJECTIVES Liposarcomas form a diverse group of tumors that represent the majority of retroperitoneal soft tissue sarcomas. Radical excision of these retroperitoneal liposarcomas is often challenging due to their large size and proximity to visceral organs and major vessels. Here we present the 30-year experience of our multidisciplinary sarcoma team in the treatment of these tumors and analysis of factors influencing survival. METHODS Patients with retroperitoneal liposarcomas treated in Helsinki University Hospital from 1987 to 2017 were reviewed. Local recurrence-free survival, metastases-free survival, and disease-specific survival were assessed with Kaplan-Meier analysis, and factors influencing survival were evaluated with Cox regression. RESULTS A total of 107 patients were identified. The median follow-up time was 5.4 years (interquartile range: 2.2-8.8 years). Local recurrence developed in 72% and metastases in 15% during follow-up. The 5-year disease-free survival was 31% and disease-specific survival was 66%. The multifactorial analysis revealed histological type and grade as predictors of disease-specific survival (P < .01) while multifocality carried a poor prognosis for local recurrence (P = .02) and higher histological grade for metastases (P < .01). CONCLUSIONS Retroperitoneal liposarcomas rarely metastasize but tend to recur locally. For tumors that have been resected with macroscopically clear margins, histological, type, and grade are significant predictors of survival.
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Affiliation(s)
- Pauliina Homsy
- Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Finland, Helsinki, Finland
| | - Ilkka Heiskanen
- Department of Gastrointestinal Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mika Sampo
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Mikko Rönty
- Department of Pathology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Erkki Tukiainen
- Department of Plastic Surgery, University of Helsinki and Helsinki University Hospital, Finland, Helsinki, Finland
| | - Carl Blomqvist
- Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
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Atypical Lipomatous Tumors: Does Our Inconsistent Terminology Have Patient Repercussions? Results of a Meta-Analysis. Am J Clin Oncol 2020; 42:487-492. [PMID: 30932920 DOI: 10.1097/coc.0000000000000540] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Misnaming low-grade lipomatous tumors poses a clinical and medicolegal challenge, potentially subjecting patients to expensive and unnecessary surgeries. The terms atypical lipomatous tumor (ALT) and "well-differentiated" liposarcoma (WDL) have been used interchangeably in pathology reports, scholarly works and consensus recommendations, creating vagaries between low-virulence extremity tumors and retroperitoneal disease with metastatic potential. METHODS A systematic review was performed on all studies that reported on the local recurrence rate and metastasis of ALTs and WDLs in living human subjects. Local recurrence and metastases were compared using Fisher's Exact Test. RESULTS In total, 20 studies evaluated ALTs (n=936), whereas 13 studied WDLs (n=626). Mean follow-up was 6.6±2.0 years (median, 7.0 y). No metastatic disease was observed among ALTs, whereas 15 patients with WDLs (2.7%, P<0.0001) had metastases. The local recurrence rate of ALTs was significantly lower than WDLs after both marginal (15.1%, 141/936 vs. 46.0%, 288/626, P<0.0001) and wide excisions (3.3%, 2/59 in ALT vs. 17.4%, 19/109, P=0.007). CONCLUSIONS ALT should be reserved for extremity lesions meeting appropriate histopathologic criteria that represent nonmetastatic disease, reducing over-diagnosis, over-treatment, and patient risk.
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28
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Rare synchronous presentation and development of retroperitoneal dedifferentiated liposarcoma and rectal adenocarcinoma. HUMAN PATHOLOGY: CASE REPORTS 2019. [DOI: 10.1016/j.ehpc.2019.200332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Guo S, Xu Y, Qian F, Ma J, Wang S, Chen P, Zong L. A recurrent giant retroperitoneal myxoid liposarcoma: a case report and literature review. Transl Cancer Res 2019; 8:2672-2676. [PMID: 35117024 PMCID: PMC8799068 DOI: 10.21037/tcr.2019.10.20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 09/12/2019] [Indexed: 11/10/2022]
Abstract
Retroperitoneal liposarcoma (RPLS) is a very rare type of tumor, accounting for less than 1% of all malignancies, especially the "large retroperitoneal liposarcoma" (GRPLS) of more than 20 kg (kilograms). Herein, we describe the treatment experience in a case of recurrent GRPLS. A 70-year-old woman was admitted with an enlarged abdomen, and computed tomography (CT) showed a large, low-density, homogeneous retroperitoneal mass (40×37×26 cm). In laparotomy, this 55×40×20 cm liposarcoma was completely removed and pathologically diagnosed as low-grade myxoid liposarcoma. The patient did not receive any adjuvant therapy, and CT showed no evidence of recurrence during follow-up.
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Affiliation(s)
- Shanshan Guo
- Department of Gastrointestinal Surgery, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
- Department of Oncology, Graduate School of Medicine, Dalian Medical University, Dalian 116044, China
| | - Yingying Xu
- Department of General Surgery, Yizhen People’s Hospital, Yizhen 211400, China
| | - Feng Qian
- Department of General Surgery, Southwest Hospital Affiliated to Army Medical University, Chongqing 400038, China
| | - Jingfan Ma
- Department of General Surgery, The First Hospital of Kunming, Kunming 650000, China
| | - Shaojun Wang
- Department of General Surgery, Yizhen People’s Hospital, Yizhen 211400, China
| | - Ping Chen
- Department of Gastrointestinal Surgery, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Liang Zong
- Department of Gastrointestinal Surgery, Northern Jiangsu People’s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 225001, China
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Shrestha M, Ando T, Chea C, Sakamoto S, Nishisaka T, Ogawa I, Miyauchi M, Takata T. The transition of tissue inhibitor of metalloproteinases from -4 to -1 induces aggressive behavior and poor patient survival in dedifferentiated liposarcoma via YAP/TAZ activation. Carcinogenesis 2019; 40:1288-1297. [PMID: 31074490 DOI: 10.1093/carcin/bgz023] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 01/09/2019] [Accepted: 02/25/2019] [Indexed: 12/17/2022] Open
Abstract
Liposarcoma (LS) is the most common soft-tissue sarcoma. Dedifferentiated liposarcoma (DDLS) shows more aggressive biological behavior than that of well-differentiated liposarcoma (WDLS), so advanced therapeutic agents based on molecular mechanism are urgently needed. Here we show that tissue inhibitors of metalloproteinases (TIMPs) from TIMP-1 to TIMP-4 are differently expressed and regulate yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) in LS. Database analysis showed high TIMP-1 expression in DDLS patients correlating with poor prognosis, but high TIMP-4 expression in WDLS patients with better prognosis. Stable TIMP-1 knockdown inactivated YAP/TAZ and inhibited proliferation, colony formation and migration in DDLS cells, which was rescued by a constitutive active YAP. However, stable overexpression of TIMP-1 showed the opposite in WDLS cells. Stable TIMP-4 knockdown activated YAP/TAZ and promoted proliferation and migration in WDLS cells, which was suppressed by YAP/TAZ inhibitor (verteporfin) or knockdown of YAP/TAZ. Recombinant TIMP-4 showed opposite results in DDLS cells. These results indicate that dedifferentiation in LS shifts the expression of TIMPs from type 4 to type 1, inducing more aggressive behavior and poor prognosis through YAP/TAZ activation, which can be prognostic markers and therapeutic targets for LS patients.
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Affiliation(s)
- Madhu Shrestha
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshinori Ando
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Chanbora Chea
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinnichi Sakamoto
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Nishisaka
- Department of Pathology Clinical Laboratory, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Ikuko Ogawa
- Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Takashi Takata
- Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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Cao Y, Zheng J, Lv C. Retracted Article: miR-199a-3p knockdown inhibits dedifferentiated liposarcoma (DDLPS) cell viability and enhances apoptosis through targeting casein kinase-1 alpha (CK1α). RSC Adv 2019; 9:22755-22763. [PMID: 35519458 PMCID: PMC9067024 DOI: 10.1039/c9ra01491h] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 10/15/2019] [Accepted: 07/03/2019] [Indexed: 12/11/2022] Open
Abstract
Dedifferentiated liposarcoma (DDLPS) is an aggressive tumor with high mortality. More insight into the biology of DDLPS tumorigenesis is needed to devise novel therapeutic approaches. Previous data showed that miRNA-199a-3p (miR-199a-3p) was strongly upregulated in DDLPS tissues. However, the biological role of miR-199a-3p in DDLPS remains unknown. In this study, we detected miR-199a-3p expression using RT-qPCR and observed that miR-199a-3p was more highly expressed in DDLPS tissues and cell lines (SW872 and LPS141). Functionally, MTT assay, flow cytometry and western blot results demonstrated that knockdown of miR-199a-3p inhibited DDLPS cell viability, enhanced apoptosis rate, and decreased expression of apoptosis-related genes Bax and cleaved caspase 3, as well as increased Bcl-2 expression in vitro. Moreover, xenograft tumors were generated and miR-199a-3p knockdown could suppress DDLPS xenograft tumor growth accompanying decreased proliferating cell nuclear antigen (PCNA) level and increased cleaved caspase 3 level in vivo. Mechanically, luciferase reporter assay and RNA immunoprecipitation (RIP) identified that CK1α was targeted and downregulated by miR-199a-3p. Expression of CK1α was lower in DDLPS tissues. Besides, there was a negative linear correlation between expressions of miR-199a-3p and CK1α in DDLPS tissues. Rescue experiments indicated that CK1α silencing could abolish the effect of miR-199a-3p knockdown on cell viability and apoptosis in DDLPS cells in vitro. In conclusion, knockdown of miR-199a-3p inhibits DDLPS cell viability and enhances apoptosis through targeting CK1α in vitro and in vivo. Our results suggest miR-199a-3p/CK1α axis may be a novel pathogen of DDLPS.
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Affiliation(s)
- Ye Cao
- Department of General Surgery, Shanghai Public Health Clinical Center No. 921 Rd. Tongxin, Hongkou 200083 Shanghai China +86-13651613217
| | - Jiajia Zheng
- Department of General Surgery, Zhongshan Hospital & Red Cross Hospital Xuhui 200030 Shanghai China
| | - Chentao Lv
- Department of General Surgery, Shanghai Public Health Clinical Center No. 921 Rd. Tongxin, Hongkou 200083 Shanghai China +86-13651613217
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Abstract
Well-differentiated liposarcoma (WDL)/atypical lipomatous tumor and dedifferentiated liposarcoma (DDL) together comprise the largest subgroup of liposarcomas, and constitute a histologic and behavioral spectrum of one disease. WDL and DDL typically occur in middle-aged to older adults, particularly within the retroperitoneum or extremities. WDL closely resembles mature adipose tissue, but typically shows fibrous septation with variable nuclear atypia and enlargement. WDL does not metastasize, but can dedifferentiate to DDL, which is associated with more aggressive clinical behavior, with a greater propensity for local recurrence and the capacity for metastasis. Although distant metastasis is rarer in DDL compared with other pleomorphic sarcomas, behavior is related to location, with a significantly worse outcome in retroperitoneal tumors. DDL typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma, and is usually a non-lipogenic sarcoma that is adjacent to WDL, occurs as a recurrence of WDL or which can arise de novo. WDL and DDL share similar background genetic aberrations; both are associated with high-level amplifications in the chromosomal 12q13-15 region, which includes the CDK4 and MDM2 cell cycle oncogenes. In addition, DDL harbor further genetic changes, particularly 6q23 and 1p32 coamplifications. While surgical excision remains the treatment mainstay with limited medical options for patients with aggressive recurrent disease or metastases, novel targeted therapies towards the gene products of chromosome 12 are being evaluated. This review summarizes the pathology of WDL and DDL, discussing morphology, immunohistochemistry, genetics and the differential diagnosis.
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Affiliation(s)
- Khin Thway
- Sarcoma Unit, Royal Marsden Hospital, 203 Fulham Road, London SW3 6JJ, United Kingdom.
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33
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Mooney KL, Kao CS. A Contemporary Review of Common Adult Non-germ Cell Tumors of the Testis and Paratestis. Surg Pathol Clin 2018; 11:739-758. [PMID: 30447839 DOI: 10.1016/j.path.2018.07.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
This article provides a comprehensive review of non-germ cell tumors of the testis and paratestis in adults, incorporating the latest 2016 World Health Organization updates. Clinical features, gross pathologic findings, key morphologic details, immunohistochemical profiles, and differential diagnoses are covered, with an emphasis on how to resolve commonly encountered, and sometimes difficult, differential diagnoses.
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Affiliation(s)
- Kelly L Mooney
- Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, L235, Stanford, CA 94305, USA
| | - Chia-Sui Kao
- Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, L235, Stanford, CA 94305, USA.
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Jung E, Fiore M, Gronchi A, Grignol V, Pollock RE, Chong SS, Chopra S, Hamilton AS, Tseng WW. Second Primary Malignancies in Patients with Well-differentiated/Dedifferentiated Liposarcoma. Anticancer Res 2018; 38:3535-3542. [PMID: 29848707 DOI: 10.21873/anticanres.12625] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 04/25/2018] [Accepted: 05/03/2018] [Indexed: 01/02/2023]
Abstract
BACKGROUND Well-differentiated/dedifferentiated (WD/DD) liposarcoma is a rare malignancy of putative adipocyte origin. To our knowledge, there have only been isolated case reports describing second primary cancer in patients with this disease. We report on a combined case series of such patients and explore the frequency of this occurrence using a national cancer database. MATERIALS AND METHODS Demographics and clinicopathological data were collected from patients with WD/DD liposarcoma who were found to have a concurrent or subsequent second primary cancer, at one of three sarcoma referral centers from 2014-2016. The Surveillance, Epidemiology and End Results (SEER) database was also queried to identify adult patients diagnosed with WD/DD liposarcoma between 1973-2012. Observed/expected (O/E) ratios of second primary malignancies among these cases were calculated by comparison to the age-adjusted cancer incidence in the general population using SEER*stat software. RESULTS In total, 26 out of 312 consecutive patients (8.3%) with WD/DD liposarcoma at our centers had a second primary cancer identified within 2 years of liposarcoma diagnosis. In the SEER database, among 1,845 patients with WD/DD liposarcoma, 75 (4.1%) had a second cancer within 2 years after liposarcoma diagnosis (O/E ratio=1.81, 99% confidence interval(CI)=1.33-2.40). Patients less than 50 years old at the time of liposarcoma diagnosis had a higher O/E ratio for second primary malignancy compared to older patients. A total of 269 patients (14.6%) developed a second cancer (O/E=1.33, 99% CI=1.15-1.54). CONCLUSION In some patients with WD/DD liposarcoma, there appears to be an increased risk of having a second primary cancer. Further validation and investigation is needed, as this finding may have implications (e.g. closer screening) for patients with this disease.
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Affiliation(s)
- Eric Jung
- Department of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA, U.S.A
| | - Marco Fiore
- Department of Surgery, IRCCS Foundation National Tumor Institute, Milan, Italy
| | - Alessandro Gronchi
- Department of Surgery, IRCCS Foundation National Tumor Institute, Milan, Italy
| | - Valerie Grignol
- Department of Surgery, The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, U.S.A
| | - Raphael E Pollock
- Department of Surgery, The James Comprehensive Cancer Center, Ohio State University, Columbus, OH, U.S.A
| | - Susan S Chong
- Department of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA, U.S.A
| | - Shefali Chopra
- Discovery Research Program, Department of Pathology and Laboratory Medicine, University of Southern California, Los Angeles, CA, U.S.A
| | - Ann S Hamilton
- Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, U.S.A
| | - William W Tseng
- Department of Surgery, University of Southern California, Keck School of Medicine, Los Angeles, CA, U.S.A.
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Wu YX, Liu JY, Liu JJ, Yan P, Tang B, Cui YH, Zhao YL, Shi Y, Hao YX, Yu PW, Qian F. A retrospective, single-center cohort study on 65 patients with primary retroperitoneal liposarcoma. Oncol Lett 2017; 15:1799-1810. [PMID: 29434876 DOI: 10.3892/ol.2017.7533] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 09/13/2017] [Indexed: 12/25/2022] Open
Abstract
Primary retroperitoneal liposarcoma (PRPLS) is the most common soft tissue malignancy of the retroperitoneum. To determine the pathological features and the curative effects of surgery in patients with PRPLS, and to elucidate key prognostic factors, the present study retrospectively analyzed the clinical cases of 65 patients with PRPLS. Immunohistochemical analysis demonstrated that vimentin and Ki-67 are better indicators for PRPLS immunohistochemical diagnosis compared with S-100 protein. S-100 protein was predominantly expressed in well-differentiated PRPLS. Positive expression of vimentin and Ki-67 were observed in almost all PRPLS samples, and Ki-67 exhibited a higher expression level in high-grade PRPLS. The level of Ki-67 expression was negatively correlated with disease-specific survival (DSS). Survival analysis revealed that the pathological subtype and histological grade were associated with DSS and local recurrence in the patients, whereas the tumor burden was associated with DSS but not local recurrence. In addition, complete tumor resection and contiguous organ resection were able to improve DSS. Microscopically positive margins did not affect DSS, whereas gross margins did. Multivariate analysis revealed that pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, and that histological grade was an independent factor for local recurrence. Patient sex and age at presentation were not independent factors associated with prognosis or local recurrence. Correlation analysis demonstrated that postoperative local recurrence significantly affected DSS, and local recurrence was the most common cause of mortality among patients. Histological grade was strongly associated with the invasion of adjacent organs but not with tumor burden. Furthermore, the tumor burden was not associated with recurrence or tumor invasion of adjacent organs. Ki-67 expression was associated with prognosis. Pathological subtype, histological grade and contiguous organ resection were independent prognostic factors, while histological grade was an independent factor which affected tumor recurrence.
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Affiliation(s)
- Yi-Xi Wu
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Jun-Yan Liu
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Jia-Jia Liu
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Peng Yan
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Bo Tang
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - You-Hong Cui
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Yong-Liang Zhao
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Yan Shi
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Ying-Xue Hao
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Pei-Wu Yu
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
| | - Feng Qian
- Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Chongqing 400038, P.R. China
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Dantey K, Schoedel K, Yergiyev O, Bartlett D, Rao UN. Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas. Hum Pathol 2017; 66:86-92. [DOI: 10.1016/j.humpath.2017.02.015] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Revised: 01/23/2017] [Accepted: 02/23/2017] [Indexed: 10/20/2022]
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Расулов Р, Rasulov R, Муратов А, Muratov A, Дворниченко В, Dvornichenko V, Мориков Д, Morikov D, Тетерина Т, Teterina T. RENAL REPLANTATION AT EXTENDED AND COMBINED RESECTION OF RETROPERITONEAL LIPOSARCOMA (CASE REPORT). ACTA BIOMEDICA SCIENTIFICA 2017. [DOI: 10.12737/article_5955e6b68fe7c7.51729388] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Родион Расулов
- Иркутская государственная медицинская академия последипломного образования
| | | | | | | | | | | | - Дмитрий Мориков
- Иркутская государственная медицинская академия последипломного образования
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Codenotti S, Vezzoli M, Monti E, Fanzani A. Focus on the role of Caveolin and Cavin protein families in liposarcoma. Differentiation 2017; 94:21-26. [DOI: 10.1016/j.diff.2016.11.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 11/15/2016] [Accepted: 11/22/2016] [Indexed: 01/06/2023]
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Bill KLJ, Casadei L, Prudner BC, Iwenofu H, Strohecker AM, Pollock RE. Liposarcoma: molecular targets and therapeutic implications. Cell Mol Life Sci 2016; 73:3711-8. [PMID: 27173057 PMCID: PMC7175098 DOI: 10.1007/s00018-016-2266-2] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2016] [Revised: 04/07/2016] [Accepted: 05/03/2016] [Indexed: 01/07/2023]
Abstract
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.
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Affiliation(s)
- Kate Lynn J Bill
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, The Ohio State University, 410W 10th Ave., Columbus, OH, 43210, USA
| | - Lucia Casadei
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, The Ohio State University, 410W 10th Ave., Columbus, OH, 43210, USA
| | - Bethany C Prudner
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, The Ohio State University, 410W 10th Ave., Columbus, OH, 43210, USA
| | - Hans Iwenofu
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
- Department of Pathology, The Ohio State University, Columbus, OH, USA
| | - Anne M Strohecker
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, The Ohio State University, 410W 10th Ave., Columbus, OH, 43210, USA
- Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH, USA
| | - Raphael E Pollock
- The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
- Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, The Ohio State University, 410W 10th Ave., Columbus, OH, 43210, USA.
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40
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Abdelfatah E, Guzzetta AA, Nagarajan N, Wolfgang CL, Pawlik TM, Choti MA, Schulick R, Montgomery EA, Meyer C, Thornton K, Herman J, Terezakis S, Frassica D, Ahuja N. Long-term outcomes in treatment of retroperitoneal sarcomas: A 15 year single-institution evaluation of prognostic features. J Surg Oncol 2016; 114:56-64. [PMID: 27076350 DOI: 10.1002/jso.24256] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Accepted: 03/28/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Retroperitoneal sarcomas are connective tissue tumors arising in the retroperitoneum. Surgical resection is the mainstay of treatment. Debate has arisen over extent of resection, changes in histological classification/grading, and interest in incorporating radiotherapy. Therefore, we reviewed our institution's experience to evaluate prognostic factors. METHODS Retrospective chart review of all primary RPS patients at Johns Hopkins Hospital from 1994 to 2010. Histologic diagnosis and grading were re-evaluated with current criteria. Prognostic factors for survival, and recurrence were assessed. RESULTS One hundred thirty-one primary RPS patients met inclusion criteria. Median survival for patients who undergo en-bloc resection to negative margins (R0/R1) is 81.7 months. Surgical margins and grade were the most important factors for survival along with age, gender, presence of metastases and resection of ≥5 organs. Five-year survival for R0/R1 resection was 60%, similar to compartmental resection. Radiotherapy significantly decreased local recurrence (P = 0.026) on multivariate analysis. Grade in leiomyosarcomas and dedifferentiation in liposarcomas dictated patterns of local versus distal recurrence. CONCLUSIONS En bloc surgical resection to R0/R1 margins remains the cornerstone of therapy and provides comparable outcomes to compartmental resections. Grade remains important for prognosis, and histology dictates recurrence patterns. Radiotherapy appears promising for local control and warrants further investigation. J. Surg. Oncol. 2016;114:56-64. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Eihab Abdelfatah
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Angela A Guzzetta
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Neeraja Nagarajan
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Christopher L Wolfgang
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Timothy M Pawlik
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Michael A Choti
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Richard Schulick
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Elizabeth A Montgomery
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Christian Meyer
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Katherine Thornton
- Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Joseph Herman
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Stephanie Terezakis
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Deborah Frassica
- Department of Radiation Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Nita Ahuja
- Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland
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Dedifferentiated Liposarcoma: Updates on Morphology, Genetics, and Therapeutic Strategies. Adv Anat Pathol 2016; 23:30-40. [PMID: 26645460 DOI: 10.1097/pap.0000000000000101] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL) form the largest subgroup of liposarcomas, and represent a morphologic and behavioral spectrum of 1 disease entity, which arises typically in middle to late adult life, most frequently within the retroperitoneum or extremities. DDL is defined as nonlipogenic sarcoma that is juxtaposed to WDL, occurs as a recurrence of WDL or which can arise de novo, and typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma. DDL have a propensity for local recurrence, whereas distant metastasis is rarer, and behavior is related to anatomic site, with retroperitoneal neoplasms showing a significantly worse prognosis. Surgical resection remains the mainstay of treatment, and medical options for patients with aggressive recurrent or metastatic disease are limited. DDL share similar genetic abnormalities to WDL, with high-level amplifications of chromosome 12q14-15, including the MDM2 and CDK4 cell cycle oncogenes, and DDL harbor additional genetic changes, particularly coamplifications of 6q23 and 1p32. Novel therapies targeted at the gene products of chromosome 12 are being tested in clinical trials. We review the pathology and genetics of DDL, discussing morphologic patterns, immunohistochemical and genetic findings, the differential diagnosis, and future therapeutic strategies.
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42
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May CD, Garnett J, Ma X, Landers SM, Ingram DR, Demicco EG, Al Sannaa GA, Vu T, Han L, Zhang Y, Kivlin CM, Bolshakov S, Kalam AA, Liu J, Zhou F, Broccoli D, Wang WL, Lazar AJ, Pollock RE, Lev D, Torres KE. AXL is a potential therapeutic target in dedifferentiated and pleomorphic liposarcomas. BMC Cancer 2015; 15:901. [PMID: 26573603 PMCID: PMC4647521 DOI: 10.1186/s12885-015-1916-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 11/06/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AXL is a well-characterized, protumorigenic receptor tyrosine kinase that is highly expressed and activated in numerous human carcinomas and sarcomas, including aggressive subtypes of liposarcoma. However, the role of AXL in the pathogenesis of well-differentiated (WDLPS), dedifferentiated (DDLPS), and pleomorphic liposarcoma (PLS) has not yet been determined. METHODS Immunohistochemical analysis of AXL expression was conducted on two tissue microarrays containing patient WDLPS, DDLPS, and PLS samples. A panel of DDLPS and PLS cell lines were interrogated via western blot for AXL expression and activity and by ELISA for growth arrest-specific 6 (GAS6) production. AXL knockdown was achieved by siRNA or shRNA. The effects of AXL knockdown on cell proliferation, migration, and invasion were measured in vitro. In addition, AXL shRNA-containing DDLPS cells were assessed for their tumor-forming capacity in vivo. RESULTS In this study, we determined that AXL is expressed in a subset of WDLPS, DDLPS, and PLS patient tumor samples. In addition, AXL and its ligand GAS6 are expressed in a panel of DDLPS and PLS cell lines. We show that the in vitro activation of AXL via stimulation with exogenous GAS6 resulted in a significant increase in cell proliferation, migration, and invasion in DDLPS and PLS cell lines. Transient knockdown of AXL resulted in attenuation of these protumorigenic phenotypes in vitro. Stable AXL knockdown not only decreased migratory and invasive characteristics of DDLPS and PLS cells in vitro but also significantly diminished tumorigenicity of two dedifferentiated liposarcoma xenograft models in vivo. CONCLUSIONS Our results suggest that AXL signaling contributes to the aggressiveness of DDLPS and PLS, and that AXL is therefore a potential therapeutic target for treatment of these rare, yet devastating tumors.
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Affiliation(s)
- Caitlin D. May
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA ,The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, Houston, TX USA
| | - Jeannine Garnett
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - XiaoYan Ma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Sharon M. Landers
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Davis R. Ingram
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Elizabeth G. Demicco
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Ghadah A. Al Sannaa
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Tona Vu
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Lixia Han
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA ,The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, Houston, TX USA
| | - Yi Zhang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Christine M. Kivlin
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA ,The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, Houston, TX USA
| | - Svetlana Bolshakov
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Azad Abul Kalam
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Juehui Liu
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Fuguo Zhou
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Dominique Broccoli
- Curtis and Elizabeth Anderson Cancer Institute, Memorial University Medical Center, Savannah, GA USA
| | - Wei-Lien Wang
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | - Alexander J. Lazar
- The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, Houston, TX USA ,Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX USA
| | | | - Dina Lev
- Department of Surgery, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Keila E. Torres
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX USA ,The University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences, Houston, TX USA
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Rat malignant fibrous histiocytoma (MFH)-derived cloned cell lines (MT-8 and MT-9) show different differentiation in mesenchymal stem cell lineage. ACTA ACUST UNITED AC 2015. [DOI: 10.1016/j.etp.2015.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma. Tumour Biol 2015; 37:2341-51. [DOI: 10.1007/s13277-015-4050-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 09/02/2015] [Indexed: 12/31/2022] Open
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Hwang JA, Yang HM, Hong DP, Joo SY, Choi YL, Park JH, Lazar AJ, Pollock RE, Lev D, Kim SJ. Gankyrin is a predictive and oncogenic factor in well-differentiated and dedifferentiated liposarcoma. Oncotarget 2015; 5:9065-78. [PMID: 25238053 PMCID: PMC4253419 DOI: 10.18632/oncotarget.2375] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Liposarcoma is one of the most common histologic types of soft tissue sarcoma and is frequently an aggressive cancer with poor outcome. Hence, alternative approaches other than surgical excision are necessary to improve treatment of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). For this reason, we performed a two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry/mass spectrometry (MALDI-TOF/MS) analysis to identify new factors for WDLPS and DDLPS. Among the selected candidate proteins, gankyrin, known to be an oncoprotein, showed a significantly high level of expression pattern and inversely low expression of p53/p21 in WDLPS and DDLPS tissues, suggesting possible utility as a new predictive factor. Moreover, inhibition of gankyrin not only led to reduction of in vitro cell growth ability including cell proliferation, colony-formation, and migration, but also in vivo DDLPS cell tumorigenesis, perhaps via downregulation of the p53 tumor suppressor gene and its p21 target and also reduction of AKT/mTOR signal activation. This study identifies gankyrin, for the first time, as new potential predictive and oncogenic factor of WDLPS and DDLPS, suggesting the potential for service as a future LPS therapeutic approach.
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Affiliation(s)
- Ju-Ae Hwang
- Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea
| | - Heung-Mo Yang
- Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea
| | - Doo-Pyo Hong
- Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea
| | - Sung-Yeon Joo
- Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Samsung Advanced Institute for Health Sciences and Technology, Graduate School, Department of Health Sciences and Technology, Sungkyunkwan University
| | - Yoon-La Choi
- Department of Pathology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Joo-Hung Park
- Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea
| | - Alexander J Lazar
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Raphael E Pollock
- Division of Surgical Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
| | - Dina Lev
- Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sung Joo Kim
- Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Department of Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Sarcoma Research Center, Samsung Medical Center, Seoul, Republic of Korea
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Zhang WD, Liu DAR, Que RS, Zhou CB, Zhan CN, Zhao JG, Chen LI. Management of retroperitoneal liposarcoma: A case report and review of the literature. Oncol Lett 2015; 10:405-409. [PMID: 26171040 DOI: 10.3892/ol.2015.3193] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Accepted: 04/21/2015] [Indexed: 11/05/2022] Open
Abstract
Retroperitoneal liposarcoma is a rare tumor with an incidence of 2.5 per million individuals. Early diagnosis is difficult as there is an absence of specific clinical presentations. The present case study reports a patient diagnosed with retroperitoneal liposarcoma who was treated by complete surgical resection and relapsed 3 months following the surgery. In addition, the clinical data of 14 patients with retroperitoneal liposarcoma were reviewed and analyzed. The mean age of the 14 patients at presentation was 54.1 (range, 36-73 years) and 5/14 patients experienced recurrence, ranging between 1 and 10 times. Of the 12 cases that reported histological subtypes, 7 were well-differentiated liposarcoma, 2 were dedifferentiated liposarcoma, 2 were myxoid liposarcoma and 1 was mixed subtype. All the patients underwent complete resection and 5 received combined multiple organs resection (3 nephrectomy, 1 sigmoid colon and 1 multiple visceral organs). However, no patients received chemotherapy or radiotherapy. In conclusion, retroperitoneal liposarcoma is a rare disease with a high rate of recurrence. Complete resection is the predominant treatment and combined resection of adjacent organs is occasionally necessary.
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Affiliation(s)
- Wei-Dong Zhang
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - DA-Ren Liu
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Ri-Sheng Que
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Chuan-Biao Zhou
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Chen-Ni Zhan
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Jian-Gang Zhao
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - L I Chen
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
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Liposarcoma with lymph node spread: a case presentation and a systematic review of the literature. Eur Surg 2015. [DOI: 10.1007/s10353-015-0314-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Liposarcomas of the posterior mediastinum: clinicopathologic study of 18 cases. Mod Pathol 2015; 28:721-31. [PMID: 25475695 DOI: 10.1038/modpathol.2014.152] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 09/15/2014] [Accepted: 09/15/2014] [Indexed: 12/14/2022]
Abstract
Sarcomas of the posterior mediastinum are rare and correspond mostly to neurogenic tumors. We studied 18 cases of liposarcoma presenting in the posterior mediastinum; because of their unusual location, some of these tumors posed difficulties for diagnosis. There were 11 men and 7 women aged 29-87 years (mean: 57). The tumors were large lobulated masses ranging from 6 to 30 cm in greatest diameter (median: 15 cm). Symptoms included cough, dysphagia, and chest pain. Four patients were asymptomatic and the tumors were discovered incidentally on chest X-rays. Histologically, 10/18 (55%) cases were atypical lipomatous tumor/well-differentiated liposarcoma, one of which harbored a smooth muscle component (lipoleiomyosarcoma); 3/18 (16%) were de-differentiated liposarcoma, one of which also harbored a smooth muscle component; 3/18 (16%) were myxoid/round cell liposarcoma; and 2/18 (11%) were pleomorphic liposarcoma. The cases of well-differentiated liposarcoma were mostly of the sclerosing type; however, five of them also showed prominent myxoid stroma closely resembling myxoid liposarcoma. Immunohistochemistry was performed in selected cases; 4/8 cases tested showed focal positivity for S-100 protein and 5/8 cases showed nuclear positivity for MDM-2. The three cases of myxoid liposarcoma were all negative for MDM2. Both cases of lipoleiomyosarcoma showed positivity for SMA and desmin in the smooth muscle component. FISH was performed in two cases of well-differentiated liposarcoma and high levels of amplification of MDM2 at 12q13-15 were observed; the CHOP translocation at 12q13.1-q13.2 was absent in both cases. Complete surgical excision was performed in 11 cases; however, negative surgical margins were achieved only in four. Clinical follow-up ranging from 1 to 192 months (median 28 months) was available for 13 patients. Two patients with myxoid/round cell liposarcoma died of tumor after 4 months and 3 years, respectively. Both had widely disseminated metastatic disease at the time of death. Six patients (6/10) with well-differentiated liposarcoma were alive and well with no evidence of disease (at 4, 7, 12, 15, and 25 months) and three (3/10) were alive with disease (at 3, 4, and 6 months). One patient with well-differentiated liposarcoma had multiple recurrences and a liver metastasis after 14 years; however, the patient was alive and well at 16 years. Five patients were lost to follow-up. In general, the biologic behavior of liposarcomas in the posterior mediastinum seems to correlate well with the histologic subtype and mirrors that of their counterpart in the retroperitoneum.
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Gronchi A, Collini P, Miceli R, Valeri B, Renne SL, Dagrada G, Fiore M, Sanfilippo R, Barisella M, Colombo C, Morosi C, Stacchiotti S, Casali PG, Dei Tos AP, Pilotti S. Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma. Am J Surg Pathol 2015; 39:383-393. [PMID: 25581729 DOI: 10.1097/pas.0000000000000366] [Citation(s) in RCA: 85] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The aim of the present work was to improve the understanding of the impact of malignancy grade and myogenic/rhabdomyoblastic differentiation on the natural course of retroperitoneal liposarcoma. All consecutive patients affected by primary well-differentiated (WD)/dedifferentiated (DD) retroperitoneal liposarcoma, surgically treated at our institution between January 2002 and December 2011, were retrospectively evaluated. Tumors were stained for mdm2 and 5 myogenic markers (smooth muscle actin-α, h-caldesmon, calponin, desmin, myogenin). The French National Federation of the Centers for the Fight Against Cancer (FNCLCC) grading system was applied. Overall survival, crude cumulative incidence of local recurrence, and distant metastases were calculated. Multivariable analyses were carried out. A total of 144 patients were identified. Median follow-up was 68 months (interquartile range: 46 to 104 mo). Fifty-two patients were affected by WD/G1 and 92 by DD liposarcoma. Among the latter, 60 were grade G2 and 32 G3. Myogenic differentiation was present in 54 cases (8/52 WD/G1, 27/60 DD/G2, 18/32 DD/G3). Seven cases had a rhabdomyoblastic DD component (1/60 DD/G2 and 6/32 DD/G3). Five-year overall survival rates were 93%, 57%, and 21% for WD/G1 liposarcoma, G2 DD, and G3 DD liposarcoma, respectively, and 75%, 42%, and 29% for liposarcoma without myogenic differentiation, with myogenic differentiation, with rhabdomyoblastic differentiation, respectively (P<0.001). Of note, 5/6 patients affected by G3 DD liposarcoma with a rhabdomyoblastic component died within 8 months. FNCLCC grade and myogenic differentiation significantly predicted the outcome of retroperitoneal liposarcoma. These should be factored into treatment decision-making and possibly used to stratify patients in clinical trials.
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Affiliation(s)
- Alessandro Gronchi
- Departments of *Surgery †Pathology ‡Biostatistics §Cancer Medicine ∥Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan ¶Department of Pathology, Azienda ULSS 9, Treviso, Italy
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Kerkhofs TM, Roumen RM, Demeyere TB, van der Linden AN, Haak HR. Adrenal tumors with unexpected outcome: a review of the literature. Int J Endocrinol 2015; 2015:710514. [PMID: 25883649 PMCID: PMC4389822 DOI: 10.1155/2015/710514] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Revised: 10/01/2014] [Accepted: 10/01/2014] [Indexed: 12/21/2022] Open
Abstract
The finding of an adrenal mass should induce a diagnostic work-up aimed at assessing autonomous hormone production and differentiating between benign and (potentially) malignant lesions. The common differential diagnosis in adrenal incidentaloma consists of (non-)functioning adenoma, pheochromocytoma, myelolipoma, metastasis, and primary carcinoma. There remains a category of lesions that are hormonally inactive and display nonspecific imaging characteristics. We provide a succinct literature review regarding pathologies from this category. Imaging and histological characteristics are discussed, as well as clinical management. In conclusion, an adrenal mass may present a diagnostic challenge. After exclusion of most common diagnoses, it can be difficult to differentiate between possible pathologies based on preoperative diagnostic tests. Surgical resection of possibly harmful tumors is indicated, for example, lesions with malignant potential or risk of spontaneous hemorrhage. Resection of an obviously benign lesion is not necessary, unless problems due to tumor size are expected.
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Affiliation(s)
- Thomas M. Kerkhofs
- Department of Internal Medicine, Máxima Medical Center, Ds. Th. Fliednerstraat 1, 5631 BM Eindhoven, The Netherlands
- *Thomas M. Kerkhofs:
| | - Rudi M. Roumen
- Department of Surgery, Máxima Medical Center, De Run 4600, 5504 DB Veldhoven, The Netherlands
- Research School GROW, School for Oncology and Developmental Biology, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands
| | - Thomas B. Demeyere
- Department of Pathology, Stichting PAMM, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
| | | | - Harm R. Haak
- Department of Internal Medicine, Máxima Medical Center, Ds. Th. Fliednerstraat 1, 5631 BM Eindhoven, The Netherlands
- Department of Internal Medicine, Division of General Internal Medicine, Maastricht University Medical Centre, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands
- Department of Health Services Research and CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, P.O. Box 616, 6200 MD Maastricht, The Netherlands
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