Dedifferentiated Component Research Articles

Retroperitoneal dedifferentiated liposarcomas: semi-quantitative assessment of the dedifferentiated component and prognosis

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. 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. 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). 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.

Ultrasonographic findings and diagnosis of omental dedifferentiated liposarcoma: a case report.

Liposarcoma is one of the most common types of soft tissue sarcomas and can develop at any site, although omental liposarcoma is extremely rare. Omental liposarcoma has a poor prognosis because the diagnosis is difficult, until it presents as a large tumor causing severe noticeable clinical symptoms. A 51-year-old male with lower abdominal pain was referred to our clinic. Abdominal ultrasonography revealed an ill-defined, solid, heterogeneous, and hypoechoic tumor deep in the lower abdomen. Generally, liposarcomas are hyperechoic, though 20% of liposarcomas present as hypoechoic tumors. This variation might occur depending on the pathological classification. We should consider the possibility of a dedifferentiated component if ultrasonography reveals typical features of soft tissue sarcoma with hypoechoic lesion.

Analysis of Dedifferentiated Liposarcomas Emphasizing the Diagnostic Dilemmas

Abstract Introduction: Dedifferentiated liposarcoma (DDLPS) is defined as a progression of well-differentiated liposarcoma (WDLPS) to another nonlipogenic sarcoma. Since a variety of heterologous sarcomas can be encountered in dedifferentiation, clinical dilemmas arise. The present study analyzed the role of clinicopathologic and immunohistochemical (IHC) features in the diagnosis of DDLPS and its differentiation from mimics. Materials and Methods: A retrospective and prospective study was conducted wherein all cases of liposarcoma from 2012 to 2017 were reviewed. DDLPS cases were identified among pleomorphic lesions. Clinical and histopathological details for these cases were retrieved from medical records section and department archives. Histomorphology and immunohistochemistry (MDM2, S100, and Ki-67) were analyzed for these cases. Results: Among 37 cases of liposarcomas reviewed, DDLPS was diagnosed in 12 cases (32.4%). Mean age of the patients was 54.3 years with equal gender distribution (M:F =1:1.2). Two patients had recurrent tumors. Most were retroperitoneal (58.3%) with mean duration of symptoms being 8.7 months. Mean tumor dimension was 17.5 cm. High-grade dedifferentiated component was most common (83.3%) with only one case each (8.3%) of low-grade and homologous dedifferentiation. Undifferentiated pleomorphic sarcoma was the frequent nonlipogenic sarcoma. MDM2 overexpression was detected in 100%, focal S100 positivity seen in 66.6%, and mean Ki-67 labeling index was 24. Conclusion: DDLPS exhibits aggressive clinical behavior. Adequate sampling, correlation to clinical details, demonstration of transition from WDLPS to DDLPS aid in narrowing the differentials. Immunostaining with MDM2 helps in definite categorization and S100 highlights lipoblasts, when they are not easily identifiable. MDM2, CDK4, and p16 IHC panel is recommended in all cases and fluorescence in situ hybridization analysis where IHC is noncontributory.

Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution.

Background Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. Methods In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. Results Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. Conclusions The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients.

Integrated exome and RNA sequencing of dedifferentiated liposarcoma

The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.

Dedifferentiated Chondrosarcoma Demonstrating Osteosarcomatous Differentiation

Background: Dedifferentiated chondrosarcoma (DDC) accounts for a small proportion of chondrosarcomas. They demonstrate aggressive behaviour with a high rate of local recurrence and systemic progression resulting in poor long-term survival rates. Due to its relatively low incidence, previous studies have grouped different histiotypes together to achieve adequate study numbers for analysis. Methods: This retrospective study examines the clinical course and the role of chemotherapy in the subgroup of patients with DDC where osteosarcoma is the predominant dedifferentiated component. Between 2000-2010, 21 patients were identified. Results: The mean age at presentation was 64 years (range 35-80 years). 12 patients were considered unfit for chemotherapy, whilst 2 patients declined chemotherapy. 5 patients received neoadjuvant chemotherapy, with less than 90% necrosis demonstrated in all these cases. 3 patients received post-operative chemotherapy. The median survival for the entire group was 9.5 months. In the 7 patients who received chemotherapy, the median survival was 17 months, and those who had chemotherapy had a greater median time to local recurrence. Conclusion: This study demonstrates that cytotoxic chemotherapy may be offered to appropriately selected patients.

Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin.

Well-differentiated (WD) liposarcoma is a low-grade mesenchymal tumor with features of mature adipocytes and high propensity for local recurrence. Often, WD patients present with or later progress to a higher-grade nonlipogenic form known as dedifferentiated (DD) liposarcoma. These DD tumors behave more aggressively and can metastasize. Both WD and DD liposarcomas harbor neochromosomes formed from amplifications and rearrangements of Chr 12q that encode oncogenes (MDM2, CDK4, and YEATS2) and adipocytic differentiation factors (HMGA2 and CPM). However, genomic changes associated with progression from WD to DD have not been well-defined. Therefore, we selected patients with matched WD and DD tumors for extensive genomic profiling in order to understand their clonal relationships and to delineate any defining alterations for each entity. Exome and transcriptomic sequencing was performed for 17 patients with both WD and DD diagnoses. Somatic point and copy-number alterations were integrated with transcriptional analyses to determine subtype-associated genomic features and pathways. The results were, on average, that only 8.3% of somatic mutations in WD liposarcoma were shared with their cognate DD component. DD tumors had higher numbers of somatic copy-number losses, amplifications involving Chr 12q, and fusion transcripts than WD tumors. HMGA2 and CPM rearrangements occur more frequently in DD components. The shared somatic mutations indicate a clonal origin for matched WD and DD tumors and show early divergence with ongoing genomic instability due to continual generation and selection of neochromosomes. Stochastic generation and subsequent expression of fusion transcripts from the neochromosome that involve adipogenesis genes such as HMGA2 and CPM may influence the differentiation state of the subsequent tumor.

Diagnostic utility of IDH1/2 mutations to distinguish dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone

Histologically, it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma (UPS) of bone when the low-grade cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are present in a significant number of cartilaginous tumors including most conventional chondrosarcomas and dedifferentiated chondrosarcomas. These mutations have not been studied in UPSs of bone. We sought to investigate whether an IDH1 or IDH2 mutation signature could be used as a clinically diagnostic marker for the distinction of dedifferentiated component of chondrosarcoma from UPS of bone. Sixty-eight bone tumor cases, including 31 conventional chondrosarcomas, 23 dedifferentiated chondrosarcomas, and 14 UPSs of bone, were collected for IDH1/2 mutation analysis either using the Qiagen IDH1/2 RGQ PCR Kit or using whole-exome sequencing. IDH1/2 mutations were detected in 87% (20/23) of dedifferentiated chondrosarcomas and 30% (6/20) of conventional chondrosarcomas. No mutations were detected in the IDH1/2 codon 132 or codon 172 among 14 UPSs of bone. Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than UPS of bone while also providing some insight into the pathogenesis of these 2 lesions.

P2.04-036 Giant Primary Dedifferentiated Liposarcoma of the Anterior Mediastinum: An Extremely Rare Occurrence: Topic: Esophageal Cancer and Other Malignancies

To present an extremely rare case of giant primary dedifferentiated liposarcoma of the anterior mediastinum. A 70-year-old male presented for persistent dyspnea. Chest CT-scan showed a huge well-defined solid mass with a fatty tissue component in the anterosuperior mediastinum (Fig. 1A). The tumor caused a wide displacement of the right lung and mediastinal organs with no signs of invasion. PET-CT scan showed a unique uptake of the mediastinal mass (Suv max=4.6). A surgical resection was proposed. A right emi clamshell incision was performed. On exploration, a huge mass of the anterior mediastinum causing the compression of the right lung, pericardium and great vessels was observed; no sign of adjacent organs invasion was found. The tumor was radically resected and the patient was discharged uneventfully after 6 days. The patient denied any adjuvant therapy. No evidence of recurrence has been identified as of 16 months postoperatively. Macroscopically, the smooth, lobulated, well demarcated, yellowish-white mass weighed 2102g and measured 27×23×13cm (Fig. 1B). Microscopically, the tumor presented a dedifferentiated component characterized by spindle cells organized in a fascicular pattern with abundant stroma and necrosis (Fig. 1C) and a second component of lipoma-like well-differentiated liposarcoma (Fig. 1D). Figure 1E showed both components. The spindle cells displayed a moderate degree of nuclear atypia, with moderate to marked levels of pleomorphism and cellularity. The spindle cells resulted positive for desmin and SMA and had an elevated proliferative index (Ki67=50%) (Fig. 1F). Immunohistochemically, tumor cells of both components were positive for CDK4 (Fig. 1G) MDM2 (Fig. 1H) and negative for myoglobin, EMA, S-100. Given that, a final pathological diagnosis of primary dedifferentiated liposarcoma of the mediastinum was disclosed. Primary dedifferentiated liposarcoma of the mediastinum is extremely rare. Chemotherapy and radiotherapy seems to be ineffective; radical surgical resection represents the best therapeutic modality. A closed and long-term follow-up is required because of the high risk of recurrence.

Non-Radiographic Risk Factors Differentiating Atypical Lipomatous Tumors from Lipomas

To determine non-radiographic risk factors differentiating atypical lipomatous tumors (ALTs) from lipomas. All patients with deep-seated lipomatous tumors of the extremities treated from January 2000 to October 2010 were retrospectively reviewed. Factors reviewed included age, gender, tumor location, size, histology, local recurrence, dedifferentiation, and metastasis. Multivariate logistic regression models were used to evaluate the effects of patient characteristics on ALT status. Ninety-four lipomas and 46 ALTs were included. Patients with an ALT were older (median: 60.5 vs. 55 years). Lipomas were evenly distributed between upper (48.9%) and lower extremities (51.1%), whereas ALTs predominately involved the lower extremities (91.3%). Median ALT size (22 cm) was greater than lipomas (10 cm), p < 0.0001. One lipoma (1.04%) recurred at 77 months and five ALTs (10.9%) recurred at an average of 39 months (19-64 months). Two ALTs originally treated with wide resection recurred with a dedifferentiated component and were treated with wide re-excision and chemotherapy. No metastases or tumor-related deaths occurred in either group at the time of last follow-up. Patients older than 60 years, tumors greater than 10 cm, or thigh location, were more likely to be diagnosed with an ALT (p < 0.05). Lipomatous tumors were more likely to be ALTs when the tumor was at least 10 cm in size, located in the thigh, or found in patients that were 60 years of age or older. These risk factors may be used to guide management and surveillance strategies, when lipomatous tumors do not display characteristic radiographic features.

Dedifferentiated Liposarcoma of Retroperitoneum With Extensive Osteosarcomatous Component

Dedifferentiated liposarcoma (DDLS) is a rare subtype of liposarcoma composed of 2 components: a well-differentiated liposarcoma (WDLS) and a nonlipogenic sarcoma (dedifferentiation component), represented in &amp;gt;90% of cases by a high grade undifferentiated pleomorphic sarcoma, in the form of both small microscopic foci and/or grossly recognizable nodular masses. The paper reports a rare case of a retroperitoneal DDLS, in which approximately half of a tumor mass is composed of a high-grade osteosarcoma. A 68-year-old Caucasian woman affected by abdominal discomfort. Clinical examination showed a large, hard and fixed abdominal mass. Computed tomography scan revealed a huge retroperitoneal mass composed of 2 distinct components: the upper part showed a hypodense tissue, while the lower part showed a higher density and coarse calcifications. Patient underwent to a challenging surgical resection of the mass that, at histological examination, resulted to be a DDLS, in which a WDLS coexisted with an osteosarcoma. Presurgical diagnosis of DDLS is difficult due to the great morphologic variability of the dedifferentiated component, ranging from low to high-grade nonlipogenic sarcoma. The present case contributes to widen the morphological spectrum of DDLS, emphasizing the possibility that a retroperitoneal mass with a dual tissue component, one of which containing extensive areas with coarse calcifications, is highly suspected to be a DDLS with an osteosarcomatous component. This pre-operative finding should alert the surgeon because it has a significant impact on prognosis, increasing the risk of local recurrence and of death by disease in a few months after diagnosis.

Managing Liposarcomas: Cutting Through the Fat.

Liposarcomas are one of the most common of more than 50 histologic subtypes of soft tissue sarcomas that, themselves, are heterogeneous. Liposarcomas fall into four distinct histologic subtypes: atypical lipomatous tumor/well-differentiated liposarcoma, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Definitive treatment remains surgical resection with negative margins for resectable disease. However, well-differentiated liposarcomas that are large or difficult to operate upon should be followed with close surveillance as long as there is no radiologic concern for a dedifferentiated component. In contrast, first-line chemotherapy with anthracycline with or without ifosfamide, or gemcitabine and docetaxel should be used for inoperable myxoid (round cell) or pleomorphic liposarcomas, which are relatively responsive to chemotherapy. In the second- and third-line setting, myxoid liposarcomas, in particular, seem to be sensitive to trabectedin, which was recently approved by the US Food and Drug Administration (FDA). Eribulin offered a survival benefit when compared with dacarbazine in the third-line setting in liposarcomas (other than the well-differentiated subtype) and is now FDA approved. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of liposarcoma subtypes but represent actionable targets. Cyclin-dependent kinase 4 and murine double minute 2 are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer opportunities that are being pursued in clinical trials. It is critical that liposarcomas are not approached by oncologists as one disease entity but rather subclassified into distinct subtypes using histologic and molecular tools before formalizing a treatment plan.

Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors.

Chordomas are slow-growing malignant neoplasms. Determination of histopathologic prognostic factors using a large cohort study has been limited by their low incidence. In this retrospective study, we investigated the clinical, histopathologic, and immunohistochemical prognostic factors in 287 chordomas from 111 patients assessed by central pathologic review. Expression patterns of a variety of markers, including vascular endothelial growth factor (VEGF), mTOR pathway, c-kit, HER2, epidermal growth factor receptor (EGFR) and STAT3, and KRAS, BRAF, EGFR, and PIK3CA mutations were analyzed. On univariate analysis, the results confirm surgery as the best treatment, as judged by patient progression-free survival (PFS) and overall survival (OS). Proton therapy, the presence of a dedifferentiated component, mitotic figures, and Ki67 and p53 labeling indices correlated with PFS . Necrosis and apoptosis correlated with OS. Based on these findings, we propose a histopathologic grading system that correlates with PFS and OS. On multivariate analysis, extent of resection, tumor grade, and proton therapy were independent prognostic factors of PFS; extent of resection, tumor location, and grade were independent prognostic factors of OS. Based on the expression of EGFR, pSTAT3, VEGF, and mTOR pathway proteins, (in 85.9%, 79.1%, 85.7%, and 46% of chordomas, respectively), and 2 new mutations in the PIK3CA gene, we also provide evidence for potential therapeutic targets.

Can Abdominal Computed Tomography Imaging Help Accurately Identify a Dedifferentiated Component in a Well-Differentiated Liposarcoma?

To assess the ability of computed tomography (CT) to differentiate an atypical lipomatous tumor/well-differentiated liposarcoma (WDLPS) from a WDLPS with a dedifferentiated component (DDLPS) within it. Forty-nine untreated patients with abdominal atypical lipomatous tumors/well-differentiated liposarcomas who had undergone contrast-enhanced CT were identified using an institutional database. Three radiologists who were blinded to the pathology findings evaluated all the images independently to determine whether a dedifferentiated component was present within the WDLPS. The CT images were evaluated for fat content (≤25% or >25%); presence of ground-glass density, enhancing and/or necrotic nodules; presence of a capsule surrounding the mass; septations; and presence and pattern of calcifications. A multivariate logistic regression model with generalized estimating equations was used to correlate imaging features with pathology findings. Kappa statistics were calculated to assess agreement between the three radiologists. On the basis of pathological findings, 12 patients had been diagnosed with DDLPS within a WDLPS and 37 had been diagnosed with WDLPS. The presence of an enhancing or a centrally necrotic nodule within the atypical lipomatous tumor was associated with dedifferentiated liposarcoma (P = 0.02 and P = 0.0003, respectively). The three readers showed almost perfect agreement in overall diagnosis (κ r = 0.83; 95% confidence interval, 0.67-0.99). An enhancing or centrally necrotic nodule may be indicative of a dedifferentiated component in well-differentiated liposarcoma. Ground-glass density nodules may not be indicative of dedifferentiation.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.

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.

Clinicopathological and Targeted Exome Gene Features of a Patient with Metastatic Acinic Cell Carcinoma of the Parotid Gland Harboring an ARID2 Nonsense Mutation and CDKN2A/B Deletion.

We describe the presentation, treatment, clinical outcome, and targeted genome analysis of a metastatic salivary acinic cell carcinoma (AciCC). A 71-year-old male presented with a 3 cm right tail of a parotid lesion, first detected as a nodule by the patient seven months earlier. He had a right total parotidectomy with cranial nerve VII resection, right facial nerve resection and grafting, resection of the right conchal cartilage, and right modified radical neck dissection. The primary tumor revealed AciCC with two distinct areas: a well-differentiated component with glandular architecture and a dedifferentiated component with infiltrative growth pattern associated with prominent stromal response, necrosis, perineural invasion, and cellular pleomorphism. Tumor staging was pT4 N0 MX. Immunohistochemistry staining showed pankeratin (+), CD56 (−), and a Ki67 proliferation index of 15%. Upon microscopic inspection, 49 local lymph nodes resected during parotidectomy were negative for cancer cells. Targeted sequencing of the primary tumor revealed deletions of CDKN2A and CDKN2B, a nonsense mutation in ARID2, and single missense mutations of unknown significance in nine other genes. Despite postoperative localized radiation treatment, follow-up whole body PET/CT scan showed lung, soft tissue, bone, and liver metastases. The patient expired 9 months after resection of the primary tumor.

The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma.

Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma. Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients. Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival. Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

Retroperitoneal Sarcoma (RPS) Target Volume and Organ at Risk (OAR) Contour Delineation Agreement Among RTOG Sarcoma Radiation Oncologists

Purpose/Objective(s)To evaluate the variability in target volume and OAR contour delineation for RPS by Radiation Therapy Oncology Group (RTOG) sarcoma radiation oncologists (ROs).Materials/MethodsRadiation planning computed tomography (CT) scans for 2 RPS cases were distributed to 12 sarcoma ROs with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high risk CTV (HR CTV: area judged to be at high risk of positive margins after resection), and OARs: bowel bag, small bowel, large bowel, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics.ResultsEach case was contoured by 11 ROs. The first case (RPS 1) was a patient with well-differentiated (WD) liposarcoma (LPS) with a de-differentiated (DD) component, and the second case (RPS 2) was a patient with DD LPS. Contouring agreement for all volumes is shown in the Table. Agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, large and small bowel was high, but agreement for duodenum was fair to moderate.ConclusionsOral Scientific Abstract 253; TableKappa Statistic Agreement for RPS Target and OAR VolumesRPS 1RPS 2Kappa Level of AgreementKappa Level of AgreementGTV0.84 Almost Perfect0.92 Almost PerfectCTV0.79 Substantial0.86 Almost PerfectHR CTV0.50 Moderate0.57 ModerateBowel Bag0.82 Almost Perfect0.79 SubstantialSmall Bowel0.73 Substantial0.78 SubstantialLarge Bowel0.73 Substantial0.82 Almost PerfectStomach0.77 Substantial0.83 Almost PerfectDuodenum0.41 Moderate0.36 Fair Open table in a new tab Purpose/Objective(s)To evaluate the variability in target volume and OAR contour delineation for RPS by Radiation Therapy Oncology Group (RTOG) sarcoma radiation oncologists (ROs). To evaluate the variability in target volume and OAR contour delineation for RPS by Radiation Therapy Oncology Group (RTOG) sarcoma radiation oncologists (ROs). Materials/MethodsRadiation planning computed tomography (CT) scans for 2 RPS cases were distributed to 12 sarcoma ROs with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high risk CTV (HR CTV: area judged to be at high risk of positive margins after resection), and OARs: bowel bag, small bowel, large bowel, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Radiation planning computed tomography (CT) scans for 2 RPS cases were distributed to 12 sarcoma ROs with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high risk CTV (HR CTV: area judged to be at high risk of positive margins after resection), and OARs: bowel bag, small bowel, large bowel, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. ResultsEach case was contoured by 11 ROs. The first case (RPS 1) was a patient with well-differentiated (WD) liposarcoma (LPS) with a de-differentiated (DD) component, and the second case (RPS 2) was a patient with DD LPS. Contouring agreement for all volumes is shown in the Table. Agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, large and small bowel was high, but agreement for duodenum was fair to moderate. Each case was contoured by 11 ROs. The first case (RPS 1) was a patient with well-differentiated (WD) liposarcoma (LPS) with a de-differentiated (DD) component, and the second case (RPS 2) was a patient with DD LPS. Contouring agreement for all volumes is shown in the Table. Agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, large and small bowel was high, but agreement for duodenum was fair to moderate. ConclusionsOral Scientific Abstract 253; TableKappa Statistic Agreement for RPS Target and OAR VolumesRPS 1RPS 2Kappa Level of AgreementKappa Level of AgreementGTV0.84 Almost Perfect0.92 Almost PerfectCTV0.79 Substantial0.86 Almost PerfectHR CTV0.50 Moderate0.57 ModerateBowel Bag0.82 Almost Perfect0.79 SubstantialSmall Bowel0.73 Substantial0.78 SubstantialLarge Bowel0.73 Substantial0.82 Almost PerfectStomach0.77 Substantial0.83 Almost PerfectDuodenum0.41 Moderate0.36 Fair Open table in a new tab

The molecular pathogenesis of dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcomas are cartilaginous tumors that consist of two distinguishable components, a lowgrade chondrosarcoma (chondrogenic) component and a highgrade dedifferentiated (anaplastic) component. The tumor cells in both components seem to originate from a single precursor, but there are a substantial number of genetic alterations in the anaplastic component. The underlying mechanism of dedifferentiation is unknown, but cell cycle regulators p16, p53 and retinoblastoma appear to have important roles in tumor development and dedifferentiation. In this article, molecular pathogenesis of dedifferentiated chondrosarcomas is reviewed.