Primary Myxofibrosarcoma Research Articles

P53 as a Potential Actionable Target in Myxofibrosarcoma: A Molecular and Pathologic Review of a Single-Institute Series

Myxofibrosarcoma (MFS) is a common adult soft tissue sarcoma characterized by high-local recurrence rate, poorly understood molecular pathogenesis, lack of specific prognostic markers, and effective targeted therapies. To gain further insights into the disease, we analyzed a well-defined group of 133 primary MFS cases. Immunohistochemical (IHC) staining for p53, MET, RET, and RB was performed. Twenty-five cases were analyzed by targeted resequencing of known cancer driver hotspot mutations, whereas 66 and 64 MFSs were examined for the presence of genetic variants in TP53 and MET gene, respectively. All clinical, histologic, immunostaining, and genetic variables were analyzed for their impact on 5-years overall survival (OS) and 5-years event-free survival (EFS). In our series, no grade I tumors relapsed and high grade are related to a positive MET immunostaining (P = .034). Both local recurrence (P = .038) and distal metastases (P = .016) correlated to the presence of “single nucleotide variant (SNV) plus copy number variation (CNV)” in TP53. Multivariate analysis revealed that age (>60 years), metastasis at presentation, and positive IHC-p53 signal are risk factors for a poor OS (P = .003, P = .000, and P = .002), whereas age (>60 years), synchronous metastasis, and tumor size (>10 cm) predict an unfavorable 5-years EFS (P = .011, P = .000, and P = .023). Considering the smaller series (n = 66) that underwent molecular screening, the presence of “SNV+CNV” in TP53 represents a risk factor for a worse 5-years EFS (hazard ratio, 2.5; P = .017). The present series confirms that TP53 is frequently altered in MFS (86.4% of cases), appearing to play an important role in MFS tumorigenesis and being a potentially drugable target. A positive p53 immunostainings is related to a poor diagnosis, and it is the presence of a single nucleotide genetic alterations in TP53 that is essential in conferring MFS an aggressive phenotype, thus supporting the use of molecular profiling in MFS to better define the role of p53 as a prognostic factor.

Analysis of clinical factors impacting recurrence in myxofibrosarcoma

Myxofibrosarcoma (MFS) is a malignant fibroblastic/myofibroblastic neoplasm with a prominent myxoid area. It has the clinical features of frequent local recurrence (LR) and occasional distant metastasis. Robust epidemiological data on MFS in China are lacking. The aim of this retrospective analysis was to determine the natural history of MFS, identify prognostic factors for recurrence and describe the real-life outcomes of MFS. We reviewed 52 patients with primary MFS from the First Affiliated Hospital of Nanjing Medical University diagnosed between 2016 and 2020. All tumors were subjected to retrospective univariate analysis for prognostic factors of the disease, including tumor size, grade, location and sex; patient age; planned operation; surgical margin; and laboratory results. The significant factors identified by univariate analysis were subsequently analyzed via multivariate analysis. Overall survival (OS), post-treatment LR and metastatic-free survival were assessed as outcomes. The median age was 61 years (range, 13–93). Fourteen (26.92%) patients exhibited low grade disease, and 38 (73.08%) exhibited high grade disease. Among the 29 males, and 23 females, 15 (28.85%) had tumors in the trunk, 37 (71.15%) had tumors in the extremities, 26 had undergone planned surgery, and 26 had unexpected unplanned operation. The margin was negative in 39 (75%) patients and positive in 13 patients (25%). The serum creatine kinase (CK) concentration was high level in 33 (63.46%) patients and low level in 19 (36.54%) patients. The serum lactate dehydrogenase (LDH) levels were low in 23 (44.23%) patients and high in 29 (55.77%) patients. LR was observed in 25 patients (48.08%), and 4 patients developed metastasis. A worse LR rate was found for patients with a low CK level (84.21%) than for those with a high CK level (27.27%) at 5 years (p < 0.05). The LR rate of patients who underwent planned surgery was lower than that of patients who underwent unplanned surgery (p < 0.05). There were significantly more patients with positive margins than patients with negative margins (92.30%, and 33.33%, respectively; p < 0.05). Moreover, superficial tumors were also associated with greater recurrence rate (2/20 [10%]) than deep tumors, (23/32 [71.86%]) [p < 0.05]. The probability of LR in patients with MFS was significantly greater in association with unplanned operations, positive margins, low serum CK levels or superficial tumor depth. These data could help identify high-risk patients; thus, more careful follow-up should be performed for higher-risk patients. Diagnosis and treatment at qualified regular medical centers can reduce the local recurrence rate of MFS.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p=.09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Ultrasonography in the assessment of primary myxofibrosarcoma in the left atrium: a case report

BackgroundCardiac myxofibrosarcoma is a rare cardiac malignant tumor, whose diagnosis is challenging due to its rare and non-specific manifestations. Ultrasound is the most important tool for detecting cardiac tumors. Yet, its diagnostic value in cardiac myxoidfibrosarcoma is rarely reported. Herein, we summarized the ultrasonic manifestations of myxofibrosarcoma in a 72-year-old Han woman.Case presentationThe patient presented with crushing chest pain without obvious inducement, lasting 3–5 min each time, which would be relieved after rest, accompanied by palpitation, chest tightness, shortness of breath, dizziness, and syncope. The electrocardiogram (ECG) suggested atrial fibrillation. Ultrasound found two moderate echogenic masses in the left atrium; one was about 48 × 31 mm in size, and the other was about 25 × 24 mm in size. The clinical diagnosis was atrial mass and atrial fibrillation. The patient underwent the operation of left atrial tumor resection + mitral valvuloplasty + atrial fibrillation radiofrequency ablation + left atrial appendectomy. The tumor was completely removed, and the patient did not receive radiotherapy or chemotherapy after surgery. The patient was reexamined by ultrasound at 6, 42, and 91 days after surgery, and no obvious abnormalities were found. On day 115, moderate echoic mass was detected on the posterior wall of the left atrium, nearing the mitral valve ring, with a size of about 28 × 23 mm. Currently, the patient is under follow-up care.ConclusionAs the most important examination method for cardiac tumors, cardiac ultrasound has good diagnostic and differential diagnosis value and can be used regularly due to its simplicity and safety. The diagnosis rate of cardiac myxofibrosarcoma can be greatly improved by summarizing the ultrasonographic manifestations of cardiac myxofibrosarcoma and differentiating them from other lesions.

Primary myxofibrosarcoma of the male breast: A case report

Myxofibrosarcoma is an unusual type of malignant fibrous histiocytoma that arises in subcutaneous tissue in the limbs of elderly patients and uncommonly involves the breast. We report a rare case of myxofibrosarcoma that occurred in a male breast. A 57-year-old man was referred to our department for a right breast mass. Physical examination revealed an irregular lump without skin involvement. Ultrasonography and mammography showed an oval and hypoechoic opacity with increased internal vascularity. The patient had a core needle biopsy that showed a sarcoma of the breast. The patient underwent a simple mastectomy. The pathology report confirmed the diagnosis of high-grade myxofibrosarcoma of the breast and the patient had local radiotherapy. After a follow-up of 18 months, the patient has no evidence of local recurrence or distant metastases. Myxofibrosrcoma of the breast is extremely rare but should be diagnosed as soon as possible because of the rapid growth of the tumor and the better prognosis in the early stages.

Establishment and characterization of NCC-MFS6-C1: a novel patient-derived cell line of myxofibrosarcoma.

Myxofibrosarcoma (MFS) is a rare and aggressive mesenchymal malignancy characterized by complex karyotypes with heterogeneous clinical features. The standard treatment for primary MFS is curative resection; however, the utility of systemic chemotherapy and radiotherapy has not been established. Although patient-derived cancer cell lines are a key bioresource for developing novel therapies, the number of MFS cell lines available from public cell banks is limited by the rarity of the disease, and large-scale drug screening has not yet been performed. To address this issue, we aimed to establish and characterize a novel MFS cell line. We successfully established a cell line, NCC-MFS6-C1, which harbors genetic abnormalities common in MFS and exhibits aggressive phenotypes such as continuous growth, spheroid formation, and invasion in tissue culture conditions. We performed drug screening using NCC-MFS6-C1 along with five MFS cell lines established in our laboratory and clarified the response spectrum of 214 existing anticancer agents. We found that two anticancer agents, gemcitabine and romidepsin, showed considerable antiproliferative effects, and these observations were concordant with the findings of our previous report, in which these agents attenuated the proliferation of five previously reported MFS cell lines. We conclude that NCC-MFS6-C1 is a useful resource for studying MFS.

Treatment strategies and outcomes of primary Myxofibrosarcomas in a large patients cohort

Backgroundthis study analysed primary myxofibrosarcoma (MFS) to investigate patient outcomes focusing on histopathologic margins and perioperative treatments. Patients and methodsdata from consecutive patients affected by primary and localized MFS of the extremities or trunk wall who underwent surgery (2002–2017) were analysed. Local recurrence (LR), amputation rate, incidence of distant metastasis (DM), and overall survival (OS) were studied. ResultsOf 293 included patients, 52 (17%) patients received perioperative treatments and 54 (18%) had positive microscopic histopathologic margins (R1). Median follow-up was 80 months (IQR, 49–109). 5-yr CCI of LR was 0.12 (SE: 0.02). Status of histopathologic margins (P < 0.001), tumour malignancy grade (P = 0.018) and size (P = 0023) were independent prognostic factor for LR. Nine amputations (amputation rate: 3%) were performed (N = 1 for primary tumour; N = 8 for LR). Larger tumour size (P = 0.015) and higher grade (P = 0.025) were independent prognostic factor for DM. 5-year OS was 0.84 (95%CI 0.79–0.88). Patient age (P = 0.008), tumour size (P = 0.013) and malignancy grade (P = 0.018) were independently associated to OS. In the subgroup of patients who had a re-excision for a primary MFS (N = 116, 40%), the presence of residual disease was not associated with LR, DM, or OS. Conclusionin this study 5-year LR, DM and OS were 12%, 17%, and 84%, respectively. One in six patients had a positive surgical margin, which was a prognostic factor for LR, while DM and OS were predicted by tumour grade and size. Findings from this large patient cohort may set benchmarks for investigating new treatment options for MFS.

Concomitant anomalous coronary artery and a large primary myxofibrosarcoma of the heart.

Concomitant anomalous coronary artery and a large primary myxofibrosarcoma of the heart.

Mesenteric Myxofibrosarcoma: A Case Report

Myxofibrosarcoma is a soft tissue sarcoma that occurs in elderly patients. Primary myxofibrosarcoma rarely arises in the mesentery; this is the fourth known case of myxofibrosarcoma presenting as a mesenteric tumor. A 62-year-old male with a mesenteric myxofibrosarcoma presented with an abdominal mass; his symptoms were frequent urination and a sense of abdominal pressure. He was admitted for further examination. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a mesenteric lesion. The preoperative diagnosis was a suspected malignant myxoid tumor. We performed a curative resection with wide margins. The histopathological and immunohistochemical findings confirmed that the tumor was mesenteric myxofibrosarcoma. The postoperative course was uneventful, and there have been no signs of relapse for three years to date after surgery. It is difficult to make a definitive diagnosis of mesenteric myxofibrosarcoma using only CT or MRI. However, when the preoperative findings suggest a malignant mesenteric tumor, then the best practice is resection with sufficient margins.

Periplocin mediates TRAIL-induced apoptosis and cell cycle arrest in human myxofibrosarcoma cells via the ERK/p38/JNK pathway

BackgroundPeriploca sepium is traditionally used in Chinese medicine to treat particularly rheumatic disorders and as a tonic. Periplocin was found as the most cytotoxic compound of its root bark and induced death receptor mediated apoptosis in liposarcoma cells. Sarcomas are a rare type of cancer with only a few treatment options. The five-year survival rate of advanced tumors is low. PurposeIn this study, we investigated the effects of periplocin in two myxofibrosarcoma (MFS)cell lines, MUG-Myx2a and MUG-Myx2b, which are subclones of the same tumor and reflect the tumor´s heterogeneity, and in T60 primary myxofibrosarcoma cells. MethodsThe xCELLigence system and the CellTiter 96® AQueous assay were used for studying cell viability. FACS and Western blot experiments were used to investigate the effects of periplocin on apoptosis induction, cell cycle distribution, and the expression of cleaved PARP, caspase 3, p53, phospho-histone γH2AX, ERK/phospho ERK, p38/phospho p38, and, finally, JNK/phospho JNK. Additionally, the expression of the apoptotic markers Bim, NOXA, Bak, Bcl-2, Bcl-xl, and the death receptors IGFR, FADD, TRADD, TNFR1A, TRAIL-R1, and TRAIL-R2 were evaluated using reversed real-time PCR. ResultsPeriplocin decreased dose-dependently the viability of all MFS cell lines and was more effective than the standard chemotherapeutic doxorubicin. It arrested the cells in the G2/M phase and led to caspase activation. Moreover, periplocin increased the mRNA expression of NOXA, Bak, Bcl-2, and death receptors such as TRAIL-R1 and TRAIL-R2 and the protein expression of ERK/phospho ERK, p38/phospho p38, and JNK/phospho JNK. In all cases, differences in the effects in the different subclones were observed. ConclusionPeriplocin showed promising effects in MFS cells. The higher effectiveness compared to doxorubicin is an important aspect for further research with regard as a treatment option. The different effects of periplocin in the two subclones showed the great importance of intratumoral heterogeneity in MFS therapy.

Grading in Myxofibrosarcoma of the Extremities Can Predict Survival and Local Control

Background: The aim of this retrospective analysis is to understand the natural history of myxofibrosarcoma (MFS), in particular whether the prognosis can be influenced by histologic grade. Methods: We reviewed 229 adult patients with primary MFS of the limbs. We analyzed disease-specific survival (overall survival [OS]) and local recurrence (LR). Results: Median age was 70 years (range, 19–92). Sixteen (7.0%) were grade 1, 38 (16.6%) grade 2, and 175 (76.4%) grade 3. A worse OS was found in grade 3 MFS (73.1%) than in grade 2 and 1 MFS (91.9 and 100%, respectively) at 5 years (p = 0.031). Locally recurred MFS had a worse OS (p = 0.018). A better LR-free rate (100% at 5 years) was observed in grade 1 MFS; however, a similar rate was observed between grade 2 and 3 tumors (77.1 and 80.0% at 5 years, respectively, p = 0.412). Conclusions: Grade 3 MFS has the worst prognosis. Grade 1 MFS have the lowest risk of LR. These data could help identify a high-risk patient group, thus selecting a more careful follow-up for higher-risk patients. Since MFS mostly affects the elderly population, it might be useful to reserve adjuvant treatments (radiotherapy and chemotherapy) to higher-risk patients.

A RARE CASE OF PRIMARY CARDIAC MYXOFIBROSARCOMA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Primary cardiac myxofibrosarcoma is a rare malignancy of mesenchymal origin which is associated with poor prognosis. Patients are generally asymptomatic in the earlier stages, however can present with life threatening hemodynamic instability. CASE PRESENTATION: Patient is a 25-year-old Caucasian male with history of asthma who presented with sudden onset of unresponsiveness, refractory shock and extensive bilateral pulmonary infiltrates. He was treated for bronchitis and pneumonia as outpatient on and off for two months prior to presentation. A transthoracic echocardiography showed large rounded mobile mass (5.5 cm by 4.5 cm) in left atrial cavity which was attached to anterior mitral leaflet causing severe mitral stenosis. CT showed extensive bilateral pulmonary consolidations. The patient was not deemed a candidate for surgical resection of the atrial mass. In the light of grave prognosis and failed aggressive medical therapy, family opted for comfort care measures. Autopsy of the left atrial mass showed low grade primary cardiac atrial myxofibrosarcoma. DISCUSSION: Myxofibrosarcoma most commonly occurs in the extremities but rarely can be seen in the heart. Primary cardiac myxofibrosarcoma is seen in the left atrium about 75% of the time [1]. Prognosis is poor because of its invasive nature and poor response to therapy including radiation, resection and chemotherapy [2]. Patients tend to be asymptomatic in the earlier stages. Clinical presentation is usually due to mass effect from the tumor. Tumor specifically located in the left atrium can cause obstruction of the mitral valve which manifests as symptoms of functional mitral stenosis leading to symptoms associated with heart failure. It can produce “tumor plop” (sound from tumor bounding around in the heart) and murmur similar to the mid-diastolic rumble of mitral stenosis [3]. This case is significant not only because of rarity of primary myxofibrosarcoma but also the clinical presentation and acute decompensation. Per our literature review, there are no reports of primary cardiac myxofibrosarcoma that presented with acute respiratory distress syndrome (ARDS). Our patient’s acute decompensation is likely synergistic result of cardiogenic shock from functional mitral stenosis (tumor mass effect) as well as underlying septic shock from pneumonia. CONCLUSIONS: Primary cardiac myxofibrosarcoma is a rare tumor which is usually detected when there are apparent hemodynamic changes form the mass effect, at which time treatment is limited given its extensive spread. Palliative care is generally the final outcome. Reference #1: Ujihira, Kosuke et al. “A case report of primary cardiac myxofibrosarcoma presenting with severe congestive heart failure” Journal of cardiothoracic surgery vol. 11,1 95. 7 Jul. 2016. Reference #2: Lazaros GA, et al. Primary myxofibrosarcoma of the left atrium: case report and review of the literature. Angiology. 2008;59(5):632–635. Reference #3: Vaideeswar, P. Butany, JW. (Feb 2008). "Benign cardiac tumors of the pluripotent mesenchyme". Semin Diagn Pathol. 25 (1): 20–8. DISCLOSURES: No relevant relationships by Bishal Bhandari, source=Web Response No relevant relationships by Cameron Koester, source=Web Response No relevant relationships by Abhishek Kalidas Kulkarni, source=Web Response No relevant relationships by Manjari Regmi, source=Web Response

Does pre-operative MRI predict the risk of local recurrence in primary myxofibrosarcoma of the extremities?

The aim of this retrospective study is to analyze and classify magnetic resonance imaging (MRI) features of primary myxofibrosarcoma (MFS) of the extremities and their correlation with patients' prognosis (local recurrence [LR] and sarcoma-specific survival [OS]). Ninety-four patients with primary MFS of the extremities were included. All MRI were performed with 1.5 Tesla magnet using a standard protocol. The presence of a "tail pattern" was recorded. Myxoid tumor component and contrast enhancement of the tumor were evaluated and graded with semiquantitative method using a newly proposed classification. A tail-like pattern was observed in 32% MFS; most of the tumors presented with high myxoid features and high grade of gadolinium (Gd) enhancement. Type 3 myxoid characteristics (P=0.003) were most often observed in FNCLCC grade 3 tumors. Estimated LR-free survival rate was 70.3% at 3 and 58.4% at 5 years. A higher LR-rate was observed in those tumors presenting a tail-like pattern at MRI (P=0.039), in those with myxoid features type 2 and 3 (0.047) and in those with Gd enhancement grade 2 or 3 (P=0.029). A worse OS was observed in Gd enhancement grade 3 (P=0.013) and in deep tumors (P=0.031). MFS features on preoperative MRI can be useful in order to identify risk classes of LR and OS. These data may suggest that patients with a tail-like pattern, high Gd enhancement and high myxoid features should be followed up more carefully after surgery.

Primary cardiac myxofibrosarcoma: case report, literature review and pooled analysis

BackgroundPrimary cardiac myxofibrosarcoma is a very rare cardiac malignancy. The majority of publications are limited to case reports. No pooled analyses of primary cardiac myxofibrosarcoma cases are available. Little clinical features and outcome patterns are acknowledged. The purpose of this study is to identify the clinical characteristics and prognostic factors of primary cardiac myxofibrosarcoma.Case presentationA case report of primary cardiac myxofibrosarcoma was presented, and a review of English language literatures of primary cardiac myxofibrosarcomas were performed electronically. Demographics, clinicopathologic data, therapy and follow-up were summarized. The median survival time and the mean survival time were calculated by Kaplan-Meier method. Survival distribution and overall survival were figured by log-rank test and cox proportional hazards models. We present a case, and retrospectively analyzed additional 30 patients derived from 24 isolated articles. The cohort consisted of 18 male and 13 female patients. The age was 41.87 ± 17.89 years. Some common features were found in clinical presentations, pathologic features, treatments and outcome patterns of primary cardiac myxofibrosarcoma. There were special features in echocardiography, histological and immunohistochemical examinations, which should be considered in diagnosis of primary cardiac myxofibrosarcoma. The median survival time/mean survival time (MST) was 14/32.66 months. The median survival time/mean survival time (MST) was 14/32.66 months. Compared to the other groups, the following groups had shorter survival characteristics, including age ≥ 40 years (14/11.79 months), female (14/26.26 months), mass diameter ≥ 40 mm (14/14.64 months), high-grade (2/11.81 months), and no post-treatment (14/28.09 months). Statistical analyses revealed that primary cardiac myxofibrosarcomas were more likely to present with local recurrences and dismal metastases. Tumors ≥ 40 mm in size (P = 0.055, HR = 6.79) or with high-grade (P = 0.063, HR = 11.45) had significantly worse prognosis.ConclusionsPrimary cardiac myxofibrosarcomas were more likely to present with local recurrences and dismal metastases. Echocardiography, together with histological method should be considered in ordinary diagnosis. Tumors ≥ 40 mm in size or with high-grade had significantly worse prognosis, which should be early diagnosed and treated with rational surgery.

Primary cardiac myxofibrosarcoma: a case report and review of the literature.

Primary myxofibrosarcoma of the heart is a rare malignancy. To the best of our knowledge, no more than 17 cases have been reported since 1963. We report the case of a 42-year-old man who presented with dyspnea and palpitation of one month's duration. Echocardiography and enhanced computed tomography revealed a large tumor in the left atrium. The patient underwent palliative excision of the tumor and histopathological analysis revealed it to be a low-grade myxofibrosarcoma. The patient developed a bone metastasis two years later and is still alive 26 months after the cardiac surgery. Primary cardiac myxofibrosarcoma involves predominantly the left atrium and the most common symptom induced by the tumor is dyspnea. Disease outcome is often disappointing despite aggressive postoperative radiotherapy and chemotherapy.

Abstract 3384: Comprehensive genetic analysis of myxofibrosarcoma and comparison with other soft tissue sarcomas

Abstract Background: Myxofibrosarcoma (MFS) is a relatively common subtype of soft tissue sarcomas (STSs) in the elderly, which is characterized by the proliferation of pleomorphic spindle cells with varying degrees of the myxoid component and on the basis of this unique histological picture, together with other clinical characteristics, is separated from other STSs. However, the genetic basis of MFS is poorly understood. Aims and Methods: The purpose of this study is to clarify the comprehensive registry of genetic alterations in MFS and other STSs using whole exome/genome sequencing (WES/WGS) of paired tumor/normal DNA from 41 samples with MFS, combined with the WES data of 25 samples with MFS and 234 with STS, which were available from The Cancer Genome Atlas (TCGA) database. WGS was performed in 2 cases. Data for DNA methylation and gene expression from the TCGA registry were also analyzed. Moreover, the genetic basis of mixed histological components characteristic of MFS and its chronological changes was interrogated using multi-regional and/or multi-time points sampling. Results: A total of 8,661 mutations were identified in WES of 66 primary MFS samples with a median of 131.2 mutations/sample, which were dominated by age-related C to T transitions at CpG sites. WGS (n = 2) detected 491 and 198 somatic structural variations in each case, which suggested MFSs have undergone complex chromosomal rearrangements. Most frequently mutated genes included TP53 (n = 19, 28.8%), ATRX (n = 10, 15.5%), and RB1 (n = 8, 12.1%), which were also detected in several types of STSs (n = 234) at similar frequencies with no mutations being specifically associated with MFS compared to other STSs. However, interestingly, STSs were reproducibly clustered into four distinct subtypes based on DNA methylation and gene expression (Cramér's V = 0.73), regardless of the histological classification. These subtypes based on DNA methylation and gene expression showed stronger correlations with the prognosis (p-value: 0.025, 0.028, respectively) than the histological classification (p-value = 0.528). Paired multi-regional sampling (n = 4) analysis disclosed high degrees of intratumor heterogeneity with less than 27% (range 9.5-26.6%) mutations being shared by different sampling. Multi-time points sampling analysis (n = 6) showed that the number of mutations did not significantly differ between primary and relapsed tumors (p-value = 0.35). There were no recurrent morphological feature-associated or relapse-specific mutational/copy number alterations. Conclusions: MFS is characterized by frequent mutations in TP53, ATRX, and RB1. STSs, including MFS, are classified into 4 distinct subgroups based on DNA methylation and gene expression, which correlated well with clinical outcomes. There were high degrees of intratumor heterogeneity in terms of mutations, which however, showed no clear correlation with morphological features. Citation Format: Yasuhide Takeuchi, Annegret Kunitz, Hiromichi Suzuki, Kenichi Yoshida, Yuichi Shiraishi, Teppei Shimamura, Kenichi Chiba, Hiroko Tanaka, Nobuyuki Kakiuchi, Yusuke Shiozawa, Akira Yokoyama, Tetsuichi Yoshizato, Kosuke Aoki, Yoichi Fujii, Hideki Makishima, Hironori Haga, Satoru Miyano, Frederik Damm, Seishi Ogawa. Comprehensive genetic analysis of myxofibrosarcoma and comparison with other soft tissue sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3384. doi:10.1158/1538-7445.AM2017-3384

Primary renal myxofibrosarcoma in a woman: A case report and literaturereview

A 45-year-old previously healthy woman presented to our hospital with a right abdominal mass. Abdominal computed tomography (CT), magnetic resonance imaging, and bone scanning revealed a 15-×10-×14-cm, welldelineated, retroperitoneal tumor originating from the right kidney. No metastases detected. The patient underwent successful extirpation of the renal tumor. The tumor showed 50% necrosis without perirenal fat infiltration, and it was diagnosed as a high-grade (grade 3) myxofibrosarcoma without nodal positivity, according to the French Federation of Cancer Centers Sarcoma (FNCLCC) grading system. Tumor immunohistochemical staining revealed positive staining for CD34, Ki67, smooth muscle actin (SMA), and cluster of differentiation 68 (CD68), and negative staining for S100 protein, desmin, mast/stem cell growth factor receptor (c-kit), and melanoma marker antibody (HMB45). Three months post-surgery, follow-up CT revealed no new abdominal metastasis, and the patient is currently receiving routine follow-up without any additional systemic therapy. Myxofibrosarcoma of the kidney is an uncommon soft tissue tumor, and radical surgery is the treatment of choice. Long-term follow-up is recommended because of the tumor’s aggressive invasiveness and potential for distant metastasis.

Report of a rare case of primary myxofibrosarcoma in the pancreatic head

Report of a rare case of primary myxofibrosarcoma in the pancreatic head

初回手術より7カ月後に左房内多発性再発を認めた心臓原発粘液線維肉腫の1例

初回手術より7カ月後に左房内多発性再発を認めた心臓原発粘液線維肉腫の1例

Myxofibrosarcoma of maxilla: A case report of rare entity

Myxofibrosarcoma is one of the most common sarcomas in the extremities of elderly patients that rarely affect the oral cavity. In this article we describe a case of primary myxofibrosarcoma of maxilla in a 19-year-old boy. Microscopically the tumor showed loosely arranged spindle-shaped tumor cells with mild pleomorphic spindle-shaped nuclei, some with minute nucleoli in a fibromyxoid stroma. The cells were strongly immunoreactive for vimentin and negative for CD-68, S-100 protein and desmin. Based on clinical, histological and immunohistochemical findings, a final diagnosis of myxofibrosarcoma was established. It is an unusual aggressive variant that frequently recurs and metastasizes, reinforcing the importance of its correct diagnosis. We report a rare case of myxofibrosarcoma in maxilla, with emphasis on immunohistochemical findings.