RESUMO
OBJECTIVE: To establish the diagnostic utility of immunohistochemistry markers p16 along with MDM2 and CDK-4 in confirming the diagnosis of well-differentiated and de-differentiated liposarcoma while taking Fluorescent in situ Hybridisation (FISH) as a gold standard. STUDY DESIGN: A cross-sectional study. Place and Duration of the Study: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from 30th January 2022 to 30th June 2023. METHODOLOGY: A standard panel of three immunohistochemistry markers p16, MDM2, and CDK4 were applied to 36 cases of atypical lipomatous tumours, well-differentiated liposarcoma (WDLPS), and de-differentiated liposarcoma (DDLPS), on which the gold standard FISH was already performed. The sample size was calculated with the help of a WHO calculator taking prevalence 1-2% in Pakistani population. Qualitative variables such as gender and site of tumour were presented by calculating frequency and percentages and comparison of Immunohistochemistry results with FISH was done by using a 2x2 table. RESULTS: The sensitivity and specificity of this triple marker panel for detecting WDLPS/DDLPS were 43.47% and 15.38%, respectively. The sensitivity and specificity of CDK4 for detecting WDLPS / DDLPS were 82.6% and 15.4%, those of MDM2 were 73.9% and 61.5 %, and those of p16 were 60.9% and 53.8%, respectively. CONCLUSION: Among all three markers, CDK4 was the most sensitive and MDM2 was the most specific marker for detecting WDLPS-DDLPS. It also showed that a combination of these three markers improves the diagnostic credibility of the immunohistochemistry in diagnosing DDLPS and WDLPS but FISH is the most reliable and confirmatory method. KEY WORDS: De-differentiated liposarcoma, Well-differentiated liposarcoma, P16, CDK4, MDM2.
Assuntos
Biomarcadores Tumorais , Quinase 4 Dependente de Ciclina , Inibidor p16 de Quinase Dependente de Ciclina , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lipossarcoma , Proteínas Proto-Oncogênicas c-mdm2 , Humanos , Lipossarcoma/diagnóstico , Lipossarcoma/patologia , Lipossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Masculino , Biomarcadores Tumorais/metabolismo , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Sensibilidade e Especificidade , IdosoRESUMO
Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-ß-high immunosuppressive tumor micro-environment.
Assuntos
Adipócitos , Evolução Clonal , Lipossarcoma , Proteínas Proto-Oncogênicas c-mdm2 , Microambiente Tumoral , Humanos , Lipossarcoma/genética , Lipossarcoma/patologia , Lipossarcoma/metabolismo , Adipócitos/patologia , Adipócitos/metabolismo , Microambiente Tumoral/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Análise de Célula Única , Feminino , Desdiferenciação Celular/genética , Masculino , Diferenciação Celular/genética , Fator de Crescimento Transformador beta/metabolismo , Pessoa de Meia-Idade , IdosoRESUMO
Dedifferentiated and Well-differentiated liposarcoma are characterized by a systematic amplification of the Murine Double Minute 2 (MDM2) oncogene. We demonstrate that p53-independent metabolic functions of chromatin-bound MDM2 are exacerbated in liposarcoma and mediate an addiction to serine metabolism to sustain tumor growth. However, the origin of exogenous serine remains unclear. Here, we show that elevated serine levels in mice harboring liposarcoma-patient derived xenograft, released by distant muscle is essential for liposarcoma cell survival. Repressing interleukine-6 expression, or treating liposarcoma cells with Food and Drugs Administration (FDA) approved anti-interleukine-6 monoclonal antibody, decreases de novo serine synthesis in muscle, impairs proliferation, and increases cell death in vitro and in vivo. This work reveals a metabolic crosstalk between muscle and liposarcoma tumor and identifies anti-interleukine-6 as a plausible treatment for liposarcoma patients.
Assuntos
Proliferação de Células , Lipossarcoma , Proteínas Proto-Oncogênicas c-mdm2 , Serina , Lipossarcoma/metabolismo , Lipossarcoma/patologia , Lipossarcoma/genética , Animais , Humanos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/genética , Camundongos , Linhagem Celular Tumoral , Serina/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Feminino , MasculinoRESUMO
BACKGROUND: Retroperitoneal liposarcoma is a rare and complex tumor originating from the mesenchymal tissues, with no specific manifestations in the early stage, and a large tumor size in the late stage. Patients often consult a physician because of large abdominal mass, increased abdominal circumference, and abdominal pain, and rarely because of leukocytosis. PATIENT CONCERNS: A 54-year-old female presented to our hospital with complaints of "abdominal distension for over 3 months, left lumbar pain for over 2 months." Considering the comprehensive symptoms, examinations, computed tomography scans, and pathological results, the possibility of retroperitoneal liposarcoma is high. DIAGNOSES: Retroperitoneal liposarcoma with leukocytosis. INTERVENTIONS: Open retroperitoneal mass excision along with transcystoscopic left ureteral Double-J Ureterl Stent Insertion tube placement and left nephrectomy. OUTCOMES: The postoperative pathological findings of the abdominal mass, combined with morphological and immunohistochemical results, are consistent with retroperitoneal liposarcoma. The patient had no recurrence in 7 months of postoperative follow-up conducted on the telephone and is now in continued follow-up. CONCLUSION: Retroperitoneal liposarcoma is highly malignant and prone to recurrence. Radical surgery is currently the primary treatment modality for patients with this condition. Analogous to cancer patients, those with elevated white blood cell counts and retroperitoneal liposarcoma may have poor prognoses, with a high likelihood of local recurrence and distant metastasis. Close postoperative follow-up is necessary. Therefore, regular postoperative review of blood routine may be a relatively economical and convenient method for the early detection of recurrence and metastasis of retroperitoneal liposarcoma.
Assuntos
Lipossarcoma , Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/patologia , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Lipossarcoma/diagnóstico , Pessoa de Meia-Idade , Feminino , Tomografia Computadorizada por Raios X , Nefrectomia/métodos , Leucocitose/etiologiaRESUMO
Naringenin (NAR) has shown potential as a cancer treatment, reducing cell proliferation and invasion in soft tissue sarcomas like liposarcoma (LPS). This study investigates NAR's role and molecular mechanism. Bioinformatic analysis was performed to assess the expression level of genes in LPS based on the GEO dataset. The heat map and PPI of genes were also analyzed. MTT, wound healing, DAPI staining, and flow cytometry evaluated the cell viability, migration, and apoptosis. Besides, real-time PCR was used to measure the NAR's impact on the expression levels of EMT, apoptosis, inflammation, and metastasis-related genes. The results showed that NAR reduces cell viability, proliferation, and migration but induces apoptosis in LPS cells. RT-PCR results revealed that NAR is capable of regulating the expression level of the apoptosis, EMT, migration, and Inflammation-related genes. This study demonstrated that NAR may play a crucial role in reducing cell viability, inducing apoptosis, and attenuating migration in Sw872 LPS cells. Consequently, NAR might be a promising and efficient factor in the treatment of LPS.
Assuntos
Apoptose , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Biologia Computacional , Flavanonas , Lipossarcoma , Flavanonas/farmacologia , Lipossarcoma/tratamento farmacológico , Lipossarcoma/patologia , Lipossarcoma/genética , Lipossarcoma/metabolismo , Humanos , Movimento Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacosRESUMO
BACKGROUND: Valid and generalizable data on the clinical features and surgical strategies for retroperitoneal liposarcoma (LPS) involving the kidney capsule remain scarce. This study aimed to investigate the clinical characteristics, morbidity, mortality, and long-term survival of patients with retroperitoneal LPS involving the kidney capsule. METHODS: The authors analyzed a prospectively maintained database of patients who underwent surgical resection for retroperitoneal LPS between 2015 and 2020. The patients were categorized into kidney capsule or no kidney capsule groups based on the presence or absence of kidney capsule involvement. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule was developed. The primary outcome measure was overall survival (OS). The cumulative event probability curve was estimated using the Kaplan-Meier, and differences between groups using the Log-Rank. RESULTS: The study population consisted of 128 patients-54 with and 74 without kidney capsule involvement. Of these patients, 70 were female (54.7%) and 58 were male (45.3%), with a median age of 55. The median follow-up duration was 35 months. Postoperative morbidity, mortality, length of hospital stay, length of ICU stay, OS, and recurrence-free survival (RFS) did not differ significantly between the groups. Eleven patients developed postoperative acute kidney injury (AKI), and one patient required dialysis during the follow-up period. In multivariable logistic regression analysis, only nephrectomy was independently associated with postoperative AKI. Subgroup analysis of patients with kidney capsule involvement showed that nephrectomy did not improve OS or RFS but significantly decreased postoperative estimated glomerular filtration rate. CONCLUSION: Nephrectomy was associated with an increased risk of postoperative AKI after retroperitoneal LPS resection. A kidney-sparing strategy for retroperitoneal LPS involving the kidney capsule achieved optimal clinical outcomes.
Assuntos
Lipossarcoma , Neoplasias Retroperitoneais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Lipossarcoma/cirurgia , Lipossarcoma/mortalidade , Lipossarcoma/patologia , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/mortalidade , Neoplasias Retroperitoneais/patologia , Idoso , Rim/cirurgia , Rim/patologia , Adulto , Nefrectomia/métodos , Nefrectomia/efeitos adversos , Complicações Pós-OperatóriasRESUMO
BACKGROUND: Retroperitoneal liposarcoma (RPLPS) is a relatively rare disease. Liposarcomas vary in size, but sizeable RPLPS larger than 30 cm in diameter are very rare, and their diagnosis and treatment present significant challenges. CASE PRESENTATION: We report a 58-year-old male patient who was admitted to the hospital with an increased abdominal circumference and was later diagnosed with a giant RPLPS. The liposarcoma was found to adhere to the right kidney and the entire ureter, invading the ascending colon. The patient underwent complete combined surgical resection. The tumor was removed intact, measured 55.0 cm × 30.0 cm × 18.0 cm, and weighed 19.8 kg. Histopathologic analysis revealed well-differentiated liposarcoma (WDLPS). The patient was successfully discharged from the hospital and followed up for 6 months with no signs of recurrence. CONCLUSION: RPLPS is a rare tumor with atypical clinical presentation. Surgery remains the most effective method of treatment for retroperitoneal sarcomas, with complete removal if there is local invasion. Preoperative examination, including three-dimensional (3D) reconstruction, is essential for surgical success. The role of adjuvant radiotherapy or chemotherapy remains controversial. However, clinicians should not rule them out as viable options.
Assuntos
Lipossarcoma , Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia , Masculino , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/patologia , Lipossarcoma/cirurgia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS). MATERIALS AND METHODS: The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32. RESULTS: Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS). CONCLUSIONS: While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.
Assuntos
Leiomiossarcoma , Lipossarcoma , Neoplasias Retroperitoneais , Trabectedina , Humanos , Leiomiossarcoma/tratamento farmacológico , Trabectedina/uso terapêutico , Trabectedina/farmacologia , Lipossarcoma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Retroperitoneais/tratamento farmacológico , Idoso , Adulto , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Alquilantes/farmacologia , Itália , Idoso de 80 Anos ou maisRESUMO
RATIONALE: Mucinous liposarcoma myxoid liposarcoma is a malignant mucoid soft tissue tumor derived from undifferentiated stromal cells in perivascular, subbody cavity and intermuscular space, and composed of cells at different stages of differentiation from preadipocytes to mature cells. In rare cases, it may change from lipoma malignancy. The main manifestations is painless mass, relatively slow growth, the course can last decades, the prevalence of liposarcoma in the population is 14% to 18%, mainly in adults, male prevalence is higher than women, but not significant. The main good hair part is the thigh, have mucinous sex, high differentiation type, dedifferentiation type, polymorphic type. Clinical diagnosis is difficult, and there are no obvious symptoms in the early stage, so the diagnosis should be combined with B ultrasound, MRI, CT, and other auxiliary examinations. The gold standard is pathological examination. In December 2023, our department admitted a patient with a mucinous abdominal mass. The report is as follows. PATIENT CONCERNS: Does liposarcoma metastasize? Is any chemotherapy required after surgery? Will it ever relapse in the future? What is the survival period after surgery? DIAGNOSIS: Mucinous liposarcoma. INTERVENTIONS: Surgical resection of the sarcoma. RESULTS: The nodule sample was 33 * 28 * 13 cm, with complete capsule, gray and yellow sections, fine texture, soft, gray, red, grayish, and yellow mucoid nodules in some areas, and the maximum diameter of the nodules was 21cm. Immunohistochemistry was: CD34 (+), CDK 4 (+), CK (-), Desmin (weak +), Ki67 (index 5%), MDM 2 (-), p16 (weak +), S-100P (+), Vimentin (+), BCL-2 (+). He was also sent to the Department of Pathology of Peking Union Medical College Hospital for consultation with Professor Lu Zhaohui, whose consultation opinion was in line with myxoliposarcoma. CONCLUSION: Retroperitoneal liposarcoma is a common retroperitoneal tumor, but it is relatively rare in clinical practice; the overall morbidity is low, mainly manifested as abdominal pain and abdominal distension, abdominal distension, and a long course of disease; it is not sensitive to radiotherapy and chemotherapy, and should be closely follow up by CT examination to understand the recurrence and metastasis.
Assuntos
Lipossarcoma Mixoide , Humanos , Masculino , Lipossarcoma Mixoide/patologia , Lipossarcoma Mixoide/diagnóstico , Lipossarcoma Mixoide/cirurgia , Lipossarcoma Mixoide/diagnóstico por imagem , Pessoa de Meia-Idade , Cavidade Abdominal/patologia , Cavidade Abdominal/diagnóstico por imagem , Lipossarcoma/patologia , Lipossarcoma/diagnóstico , Lipossarcoma/cirurgiaRESUMO
ABSTRACT: Atypical spindle cell/pleomorphic lipomatous tumor is categorized as a benign lipomatous tumor, but various MRI findings pose accurate diagnostic challenges. In our case, both MRI and PET/CT scans indicated the possibility of atypical lipomatous tumor/well-differentiated liposarcoma or dedifferentiated liposarcoma. Needle biopsy suggested benign to low-grade malignancy; hence, we opted for the wide resection. The final diagnosis of atypical spindle cell/pleomorphic lipomatous tumor was confirmed through histopathology analysis, including immunohistochemistry and fluorescence in situ hybridization. Since achieving an accurate diagnosis solely through imaging can be challenging, histopathology remains essential.
Assuntos
Lipoma , Imageamento por Ressonância Magnética , Coxa da Perna , Humanos , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/patologia , Diagnóstico Diferencial , Lipoma/diagnóstico por imagem , Lipoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Masculino , Lipossarcoma/diagnóstico por imagem , Lipossarcoma/patologia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
ABSTRACT: Among liposarcomas, well-differentiated liposarcoma and dedifferentiated liposarcoma are the most common. The majority of these tumors are found in deep retroperitoneum or extremities. When found outside the retroperitoneum, these adipose-derived tumors are known as atypical lipomatous tumors (ALT). Superficial ALT are particularly rare; thus, little is known about their clinical presentation, genomic status, and management. Here, we present the case of a 54-year-old man with an intermittently bothersome, slowly growing mass on his left upper back for over 2 years, which was incidentally diagnosed as ALT. This patient's ALT, however, showed a profound degree of pleomorphism with MDM2 and control centromere 12 (CEP12) coamplification and negative CD34 and S100 and RB1 expression, unlike most other ALT described in the literature. This case report details the diagnostic workup and histopathological findings for adipose tumors and summarizes the different subtypes, including atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, and spindle cell/pleomorphic lipoma, with brief discussion on management.
Assuntos
Lipossarcoma , Humanos , Masculino , Pessoa de Meia-Idade , Lipossarcoma/patologia , Lipossarcoma/genética , Lipoma/patologia , Biomarcadores Tumorais/análise , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Imuno-HistoquímicaRESUMO
PURPOSE: Cure models are a useful alternative to Cox proportional hazards models in oncology studies when there is a subpopulation of patients who will not experience the event of interest. Although software is available to fit cure models, there are limited tools to evaluate, report, and visualize model results. This article introduces the cureit R package, an end-to-end pipeline for building mixture cure models, and demonstrates its use in a data set of patients with primary extremity and truncal liposarcoma. METHODS: To assess associations between liposarcoma histologic subtypes and disease-specific death (DSD) in patients treated at Memorial Sloan Kettering Cancer Center between July 1982 and September 2017, mixture cure models were fit and evaluated using the cureit package. Liposarcoma histologic subtypes were defined as well-differentiated, dedifferentiated, myxoid, round cell, and pleomorphic. RESULTS: All other analyzed liposarcoma histologic subtypes were significantly associated with higher DSD in cure models compared with well-differentiated. In multivariable models, myxoid (odds ratio [OR], 6.25 [95% CI, 1.32 to 29.6]) and round cell (OR, 16.2 [95% CI, 2.80 to 93.2]) liposarcoma had higher incidences of DSD compared with well-differentiated patients. By contrast, dedifferentiated liposarcoma was associated with the latency of DSD (hazard ratio, 10.6 [95% CI, 1.48 to 75.9]). Pleomorphic liposarcomas had significantly higher risk in both incidence and the latency of DSD (P < .0001). Brier scores indicated comparable predictive accuracy between cure and Cox models. CONCLUSION: We developed the cureit pipeline to fit and evaluate mixture cure models and demonstrated its clinical utility in the liposarcoma disease setting, shedding insights on the subtype-specific associations with incidence and/or latency.
Assuntos
Lipossarcoma , Humanos , Lipossarcoma/patologia , Lipossarcoma/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Modelos de Riscos Proporcionais , Software , AdultoRESUMO
Spermatic cord malignancies are a scarce modality and liposarcoma of spermatic cord is even a rarer condition encountered. Liposarcoma is usually a slowly progressive, non-tender, well circumscribed mass of variable shapes owing to conformity to fascial compartments. We are reporting a case of 65-year-old male, with a two-month history of initially tender and later non-tender mass in the scrotum, above the testis. Ultrasonography showed a right mid inguinal mass measuring 6x3x3 cm at the superior pole of the right testis and small fluid around the right testis. Fine needle aspiration cytology (FNAC) of the right inguinal mass revealed a spindle cell neoplasm. The patient underwent right inguinal radical orchiectomy with local wide excision of the sarcoma of the spermatic cord origin. Final histopathology confirmed dedifferentiated liposarcoma. No adjuvant treatment was offered and the patient was put on surveillance. Follow-up of more than 10 months has not revealed any local recurrence, regional or non-regional lymph nodes, or systemic metastasis.
Assuntos
Neoplasias dos Genitais Masculinos , Lipossarcoma , Orquiectomia , Cordão Espermático , Humanos , Masculino , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Lipossarcoma/diagnóstico por imagem , Cordão Espermático/patologia , Cordão Espermático/diagnóstico por imagem , Cordão Espermático/cirurgia , Idoso , Neoplasias dos Genitais Masculinos/patologia , Neoplasias dos Genitais Masculinos/cirurgia , Neoplasias dos Genitais Masculinos/diagnóstico por imagem , Orquiectomia/métodos , Biópsia por Agulha FinaRESUMO
A man in his 70s presented with a left inguinoscrotal mass. Testicular tumour markers showed markedly elevated human chorionic gonadotropin (hCG). The 24.5 cm mass was resected, and histology confirmed a rare diagnosis of paratesticular dedifferentiated liposarcoma (DDLPS) with rhabdomyosarcomatous differentiation. The patient expired with distant metastasis 11 months after presenting to his general practitioner.HCG-producing soft tissue sarcomas (STS) are commonly reported as high-grade, poorly differentiated and with a poor prognosis. The role of hCG in tumour angiogenesis may influence these features.Paratesticular STS treatment guidelines have been influenced by the management of retroperitoneal STS, which are relatively more common. Studies of genitourinary STS demonstrate that positive surgical margins pose the greatest risk to local recurrence and metastasis-free survival.This case demonstrates the rapid growth of DDLPS-producing hCG, the propensity to metastasise, and poor prognosis, requiring further research into the benefit of adjuvant radiotherapy for DDLPS.
Assuntos
Gonadotropina Coriônica , Lipossarcoma , Rabdomiossarcoma , Neoplasias Testiculares , Humanos , Masculino , Lipossarcoma/patologia , Gonadotropina Coriônica/sangue , Neoplasias Testiculares/patologia , Idoso , Evolução FatalRESUMO
Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS.
Assuntos
Lipossarcoma , Humanos , Lipossarcoma/tratamento farmacológico , Lipossarcoma/terapia , Lipossarcoma/patologia , Lipossarcoma/genética , Terapia de Alvo Molecular , Imunoterapia/métodos , Medicina de Precisão/métodos , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Antineoplásicos/uso terapêuticoRESUMO
PURPOSE: Radical resection of retroperitoneal liposarcoma (RLPS) may necessitate vascular resection and reconstruction. The study was conducted to assess surgical outcomes of surgery for RLPS with major vascular involvement. METHODS: Patients with RLPS who underwent surgical resection at the Sarcoma Center of Peking University Cancer Hospital between April 2011 and December 2022 were identified from a prospectively maintained database. Patients were classified into two groups: vascular resection and non-vascular resection groups. A propensity score matching analysis was performed to eliminate baseline differences between the groups. Surgical details and postoperative outcomes were analyzed. Furthermore, prognostic factors for local recurrence-free survival (LRFS) and overall survival (OS) were assessed. RESULTS: Overall, 199 patients were identified and the median follow-up period was 48 (interquartile range [IQR] 45-69) months. Vascular resection was performed in 42 (21%) patients, 25 of whom had vascular infiltration. A total of 39 patients had vascular replacement and 3 patients underwent partial resection (side-wall resection). Vascular resection was burdened by higher rates of major morbidity (38% vs. 14%, p < 0.001) and 30-day mortality (7.1% vs. 1.3%, p = 0.005). After propensity-matched analysis, patients who underwent vascular resection had 5-year LRFS and OS rates comparable to those without vascular involvement. Major vascular resection was not an independent risk factor for LRFS or OS. CONCLUSIONS: Although accompanied by increased risks of major morbidity and mortality, the major vascular resection enabled radical resection in patients with advanced RLPS, affording comparable 5-year LRFS and OS rates compared to those who did not.
Assuntos
Lipossarcoma , Pontuação de Propensão , Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/mortalidade , Masculino , Feminino , Lipossarcoma/cirurgia , Lipossarcoma/patologia , Lipossarcoma/mortalidade , Pessoa de Meia-Idade , Idoso , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Prognóstico , Hospitais com Alto Volume de AtendimentosRESUMO
OBJECTIVE: Lipomatous soft tissue tumors (STT), ranging from benign lipomas to malignant liposarcomas, require accurate differentiation for timely treatment. Complementary to MRI, Contrast-enhanced ultrasound (CEUS) is emerging as a promising tool, providing insight into tumor microperfusion in real-time. This study aims to explore the potential of preoperative CEUS in differentiating benign lipomatous tumors from malignant liposarcoma subtypes. METHODS: Eighty-seven patients with lipomatous STT scheduled for surgery were enrolled. Clinical and MRI assessments were conducted to obtain general tumor characteristics. CEUS was used for a standardized tumor perfusion evaluation. Perfusion analysis included peak enhancement, rise time, wash-in perfusion index, and wash-out rate, reflecting the perfusion kinetics. Histopathological results were obtained for every STT and compared to perfusion characteristics. RESULTS: In total, 48 lipoma, 23 ALT and 11 liposarcoma were identified. Significant differences in tumor microperfusion were demonstrated, with higher perfusion levels indicating higher malignancy (Peak enhancement [a.u.] of Lipoma: 145 ± 238; ALT: 268 ± 368; Liposarcoma: 3256 ± 4333; p (ALT vs. Liposarcoma) < 0.001). A perfusion-based identification of a benign lipoma or ALT versus sarcoma resulted in a positive predictive value of 93%. Patient-related factors (age, gender, BMI, ASA score, smoking status) had no significant impact on the CEUS-based perfusion parameters. CONCLUSION: Our study suggests CEUS as a capable non-invasive tool for improving preoperative assessment of lipomatous STT. It can assist in the distinction between benign and malignant STT, accelerating treatment decisions and enhancing patient outcomes. Significant correlations between CEUS-derived parameters and malignancy highlight its risk assessment potential.
Assuntos
Meios de Contraste , Lipoma , Lipossarcoma , Ultrassonografia , Humanos , Lipossarcoma/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Lipoma/diagnóstico por imagem , Idoso , Ultrassonografia/métodos , Adulto , Diagnóstico Diferencial , Aumento da Imagem/métodos , Idoso de 80 Anos ou mais , Neoplasias de Tecidos Moles/diagnóstico por imagem , Estudos ProspectivosRESUMO
BACKGROUND: As a common soft tissue sarcoma, liposarcoma (LPS) is a heterogeneous malignant tumor derived from adipose tissue. Due to the high risk of metastasis and recurrence, the prognosis of LPS remains unfavorable. To improve clinical treatment, a robust risk prediction model is essential to evaluate the prognosis of LPS patients. METHODS: By comprehensive analysis of data derived from GEO datasets, differentially expressed genes (DEGs) were obtained. Univariate and Lasso Cox regressions were subsequently employed to reveal distant recurrence-free survival (DRFS)-associated DEGs and develop a prognostic gene signature, which was assessed by Kaplan-Meier survival and ROC curve. GSEA and immune infiltration analyses were conducted to illuminate molecular mechanisms and immune correlations of this model in LPS progression. Furthermore, a correlation analysis was involved to decipher the therapeutic significance of this model for LPS. RESULTS: A six-gene signature was developed to predict DRFS of LPS patients and showed higher precision performance in more aggressive LPS subtypes. Then, a nomogram was further established for clinical application based on this risk model. Via GSEA, the high-risk group was significantly enriched in cell cycle-related pathways. In the LPS microenvironment, neutrophils, memory B cells and resting mast cells exhibited significant differences in cell abundance between high-risk and low-risk patients. Moreover, this model was significantly correlated with therapeutic targets. CONCLUSION: A prognostic six-gene signature was developed and significantly associated with cell cycle pathways and therapeutic target genes, which could provide new insights into risk assessment of LPS progression and therapeutic strategies for LPS patients to improve their prognosis.
Assuntos
Regulação Neoplásica da Expressão Gênica , Lipossarcoma , Microambiente Tumoral , Humanos , Lipossarcoma/genética , Lipossarcoma/imunologia , Lipossarcoma/patologia , Lipossarcoma/mortalidade , Prognóstico , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Transcriptoma , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Nomogramas , Masculino , Feminino , Estimativa de Kaplan-Meier , Curva ROCRESUMO
BACKGROUND: Retroperitoneal liposarcoma (RLPS) constitutes the majority of retroperitoneal sarcomas. While surgical resection remains the sole curative approach, determining the optimal surgical strategy for RLPS remains elusive. This study addresses the ongoing debate surrounding the optimal surgical strategy for RLPS. METHODS: We recruited 77 patients with RLPS who underwent aggressive surgical policies. Patients were categorized into three surgical subtypes: suprapancreatic RLPS, pancreatic RLPS, and subpancreatic RLPS. Our standardized surgical strategy involved resecting macroscopically uninvolved adjacent organs according to surgical subtypes. We collected clinical, pathological and prognostic data for analyses. RESULTS: The median follow-up was 45.5 months. Overall survival (OS) and recurrence-free survival (RFS) were significantly correlated with multifocal RLPS, pathological subtype, recurrent RLPS and histological grade (P for OS = 0.011, 0.004, 0.010, and < 0.001, P for RFS = 0.004, 0.001, < 0.001, and < 0.001, respectively). The 5-Year Estimate OS of well-differentiated liposarcoma (WDLPS), G1 RLPS, de novo RLPS and unifocal RLPS were 100%, 89.4%, 75.3% and 69.1%, respectively. The distant metastasis rate was 1.4%. The morbidity rates (≥ grade III) for suprapancreatic, pancreatic, and subpancreatic RLPS were 26.7%, 15.6%, and 13.3%, respectively. The perioperative mortality rate is 2.6%. CONCLUSIONS: Standardized aggressive surgical policies demonstrated prognostic benefits for RLPS, particularly for G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS. This approach effectively balanced considerations of adequate exposure, surgical safety, and thorough removal of all fat tissue. G1 RLPS, WDLPS, unifocal RLPS, and de novo RLPS could be potential indications for aggressive surgical policies.