Surgery Treatment Improved the Overall Survival Rate in Locoregional Myxoid Leiomyosarcoma than Other Myxosarcomas in the United States.

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975-2016. Our results indicated that elderly patients and females were more in locoregional myxoid leiomyosarcoma than myxoid liposarcoma and myxoid chondrosarcoma with locoregional metastasis. The white race represented the most patients who suffered from these cancers than other races. The heart is the primary site for the abovementioned cancers, in addition to the female genitals to the myxoid leiomyosarcoma. Myxoid liposarcoma and myxoid chondrosarcoma patients with locoregional metastasis were suffering from grade II, while locoregional myxoid leiomyosarcoma patients with blank grading were due to missed data. Surgery was the most common treatment modality in this study compared with radiotherapy and chemotherapy. Kaplan-Meier analysis showed a significant difference in survival time between the three subtypes by using histology, and myxoid leiomyosarcoma showed prolonged survival than others. Elderly, female, white, unknown grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among these cancers. Multivariate analysis also showed significant differences in overall survival between the three tumors by histology, and myxoid leiomyosarcoma was with a better prognosis than others. Multivariate analysis of locoregional myxoid leiomyosarcoma showed the statistical significance of black race, grade, and radiotherapy, indicating them as independent prognostic factors of locoregional myxoid leiomyosarcoma. We conclude that surgery was the primary treatment modality against these cancers than radiotherapy and chemotherapy. And the locoregional myxoid leiomyosarcomas showed a better prognosis and higher survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma.

Systemic Inflammation Is Associated with Oncological Outcome in Patients with High-Grade Myxofibrosarcoma of the Extremities: A Retrospective Analysis.

BACKGROUND: The aim of this retrospective study is to verify whether preoperative systemic inflammatory markers (serum C-reactive protein [CRP] and neutrophil-lymphocyte ratio [NLR]) can help in predicting the disease-specific survival (DSS) and local recurrence (LR) rate in adult patients affected by localized myxofibrosarcoma (MFS) of the extremities. METHODS: We reviewed 126 adult patients with primary, localized MFS of the limbs. We analyzed DSS and LR. RESULTS: Median age at the time of surgery was 68 years (range 19-92). Median CRP was 0.4 mg/dL and median NLR was 2.8. A worse DSS was found in patients who had preoperative CRP >0.5 mg/dL (p = 0.002) and in those with NLR >3.5 (p < 0.001). In multivariate analysis, tumor size and grade as well as preoperative CRP values and NLR were confirmed to be prognostic factors in terms of DSS. An increased risk of LR was found in multivariate analysis in patients with a tail sign and with high gadolinium enhancement at preoperative MRI. CONCLUSIONS: Patients with high preoperative CRP and NLR levels, as well as large and high-grade tumors, might be considered as candidates for additional, more aggressive treatment approaches or more stringent follow-up schedules.

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.

Localized Myxofibrosarcomas: Roles of Surgical Margins and Adjuvant Radiation Therapy.

PURPOSE: The objective of this study was to describe the outcome and prognostic factors for adults treated for localized myxofibrosarcoma. METHODS AND MATERIALS: We conducted a retrospective multicenter study of 425 nonmetastatic patients who underwent surgery between January 1996 and December 2015 in French National Group and were enrolled in the Conticabase. Pathologic diagnosis was systematically reviewed by expert pathologists. The endpoints were relapse-free and metastasis-free survival. Log-rank tests and Cox models have been used to identified prognostic factors. RESULTS: Median age was 66 years; 53% were males; 85% of cases occurred in limbs or superficial trunk; median size was 60 mm; 47% and 39% were grades 2 and 3, respectively; 66% had R0 resection and 34% R1 resection. Adjuvant radiation therapy was given to 65% of patients, neoadjuvant radiation therapy to 3%, neoadjuvant chemotherapy to 7%, and adjuvant chemotherapy to 13%. The median follow-up was 51 months. The 5-year local relapse-free survival was 67%; independent prognostic factors for local relapse were R1 resection (hazard ratio [HR] = 1.26; P = .001) and adjuvant radiation therapy (HR = 0.35; P = .0001) (ie, R1 resection and no adjuvant radiation therapy increase the hazard ratio). In stratified analysis, adjuvant radiation therapy was beneficial after R0 resection (P = .0020) and after R1 resection (P = .0001). The 5-year overall survival was 80%. The 5-year metastasis-free survival was 83%. Independent prognostic factors for metastatic relapse were grade 3 disease (HR = 1.975; P = .0001) and tumor size (HR = 1.006; P = .001). CONCLUSIONS: This large series of myxofibrosarcoma confirms the high rate of local relapse. Combination of R0 resection and adjuvant radiation therapy provided the best local control. In parallel with an increasing rate of R0 resection and adjuvant radiation therapy, we observed a constant improvement in both metastatic and local relapse-free survival during the study.

Soft tissue myxofibrosarcoma: A clinico-pathological analysis of a series of 75 patients with emphasis on the epithelioid variant.

BACKGROUND AND OBJECTIVES: The clinical course of soft tissue myxofibrosarcoma is characterized by a high incidence of recurrences and there is no agreement on how to identify patients at major risk. An epithelioid histological variant has been described, with a possible worse prognosis. We reviewed our series to identify prognostic factors and assess clinical significance of the epithelioid variant. METHODS: We examined the clinico-pathological features of a series of 75 patients affected by soft tissue myxofibrosarcoma at a mean follow-up of 63 months (range 17-132). RESULTS: Disease specific survival and local recurrence free survival were, respectively, 84.8% and 76.8% at 5 years. Seven patients (8.6%) presented with the epithelioid variant with a survival of 62.5%. High grade and epithelioid morphology were negative prognostic factors for patient survival, high grade, and inadequate surgical margins for local recurrence. Radiotherapy had a local protective effect in high grade tumors. CONCLUSIONS: Our experience confirms the difficulties in obtaining wide margins in myxofibrosarcoma and the high rate of recurrence. Local recurrences did not significantly affect survival and a limb-sparing approach can be chosen also in recurrences. Patients affected by the epithelioid variant showed a worse prognosis. Chemotherapy should be considered as adjuvant treatment in this subtype. J. Surg. Oncol. 2016;114:50-55. © 2016 Wiley Periodicals, Inc.

Recurrent amplification at 7q21.2 Targets CDK6 gene in primary myxofibrosarcomas and identifies CDK6 overexpression as an independent adverse prognosticator.

BACKGROUND: Myxofibrosarcoma is genetically complex and remains obscure in molecular determinants of clinical aggressiveness. Our prior study revealed recurrent gains of 7q in myxofibrosarcomas where MET and CDK6 genes displayed increased DNA copies. Previously, we demonstrated the implication of MET overexpression, prompting us to further elucidate the roles of CDK6 in myxofibrosarcomas. MATERIALS: On tissue microarrays, CDK6 immunoexpression was assessable in 77 primary tumors, 55 of which were successfully quantified for CDK6 and MET genes by real-time PCR using genomic DNA extracted from laser-microdissected tumor cells. Gene status and protein expression of CDK6 were correlated with each other, clinicopathological variables, metastasis-free survival (MFS), and disease-specific survival (DSS). RESULTS: Protein overexpression and gene amplification of CDK6, which were detected in 21 of 77 (27.2 %) and 13 of 55 cases (23.6 %), respectively, were highly related to each other (p < .001) and associated with higher grades (overexpression, p = .004; amplification, p = .014). There was a strong correlation between CDK6 and MET gene copies (p < .001, r = 0.0714). Importantly, CDK6 protein overexpression (MFS, p = .0002; DSS, p = .0015) and gene amplification (MFS, p = .0001; DSS, p = .0083) were both univariately associated with worse outcomes. Together with nonextremity location and AJCC stage III disease, CDK6 overexpression independently portended inferior MFS (p = .0015, risk ratio [RR] = 7.411). This aberration, along with nonextremity location, was also an independent adverse prognosticator of DSS (p = .0069, RR = 6.006). CONCLUSIONS: In approximately a quarter of primary myxofibrosarcomas, CDK6 overexpression is mostly driven by gene amplification on 7q, associated with adverse prognosticators, and independently predictive of worse outcomes, highlighting its possible causative role in tumor aggressiveness.

Prognostic factors of myxofibrosarcomas: implications of margin status, tumor necrosis, and mitotic rate on survival.

BACKGROUND: Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis. METHODS: Seventy primary localized MFS were analyzed for local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS). Follow-up was obtained in 61 cases. RESULTS: Thirty-eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5-year LRFS-, MeFS-, and DSS-rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses >or=20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis >or=10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses >or=20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41). CONCLUSIONS: Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits.

Low-grade myxofibrosarcoma: a clinicopathologic analysis of 49 cases treated at a single institution with simultaneous assessment of the efficacy of 3-tier and 4-tier grading systems.

Grading of myxofibrosarcoma (MFS) is contentious and based on a variety of factors, such as the percentage of myxoid or solid areas, tumor necrosis, mitotic counts, and so on. These factors are often used in combination for different grading schemes, which have not been uniformly evaluated by consistent criteria for patients treated and prospectively followed up at a single institution. Because only a subset of low-grade (LG) MFS will progress to high grade and metastasize after relentless local recurrences, we analyze various histologic parameters and grading methods to identify prognostic predictors of the LGMFS. Forty-nine cases were classified as LGMFS after review, by using > or =30% of myxoid component, but < or =20% of solid areas and only focal, < or =10%, of tumor necrosis as cutoffs, as modified from a 2-tier system that is used in our hospital. These cases were also graded in parallel by French Federation of Cancer Centers Sarcoma Group (FNCLCC) 3-tier and 4-tier grading schemes. The study cohort consisted of 26 men and 23 women, with a median age of 60.5 years. Nineteen cases were superficial, and 30 were deep seated, with the most common site being the lower limb (57%), followed by the upper limb (31%), trunk (8%), and head and neck (4%). The primary tumors ranged from 1.5 to 24 cm in size. Solid areas (5% to 20%) were seen in 23 cases, tumor necrosis (5% to 10%) was observed in 4 cases, and a predominant myxoid area (> or =75%) was noted in 22 cases. Mitotic activity ranged from 0 to 16 (median, 2) per 10 HPF. Comparing FNCLCC 3-tier versus 4-tier grading, respectively, 26 versus 10 tumors were classified as grade I, and 23 versus 39, as grade II, with 16 cases (33%) graded discordantly by 2 schemes. A median follow-up of 55 months in 49 patients (range, 9 to 171 months) revealed local recurrence occurring in 28 patients (57%), 15 and 7 of which developed multiple local recurrences and distant metastases, respectively. There was only 1 case with pulmonary metastasis without a prior local recurrence. Currently, 33 patients are alive with no evidence of disease, 4 are alive with disease, 9 are dead of disease, and 3 are dead of unknown causes. The 5-year recurrence-free survival, metastasis-free survival (MeFS), and disease-specific mortality (DSM) rates were 41%, 90%, and 4.4%, respectively. Size of larger than 5 cm (P = 0.032), tumor necrosis (P = 0.033), and < 75% of myxoid area (P = 0.042) were significant risk factors for DSM; the former two (P = 0.011 for size larger than 5 cm, P = 0.038 for necrosis) were also significantly related to MeFS. Both FNCLCC 3-tier and 4-tier schemes failed to show a significantly better outcome in grade I LGMFS than grade II lesions with respect to all 3 endpoints. In conclusion, our data statistically validated the previous impression that even the blandest LGMFS still carries a recurrent potential that cannot be foreseen by either different grading schemes or other clinicopathologic parameters. However, DSM rate is significantly related to tumor necrosis, large size, and decreased myxoid area. Tumors having necrosis or exceeding 5 cm are at significant risk of metastatic relapse.

Myxoid synovial sarcoma: an underappreciated morphologic subset.

Focal myxoid change is a well-recognized feature of synovial sarcoma, but the presence of a predominantly myxoid stroma is rare. We describe seven cases of myxoid synovial sarcoma in which marked myxoid change initially obscured the diagnosis, leading to confusion (principally with malignant peripheral nerve sheath tumor). The median age (20 yr) and tumor location (four lower extremity, two upper extremity, and one head and neck region) were similar to those found in typical synovial sarcoma. Histologically, five cases were monophasic spindle cell lesions with a lacy appearance in areas with a prominent Alcian blue-positive myxoid stroma. Each case had foci with more typical features of synovial sarcoma, including a fascicular growth pattern with a variably collagenized stroma, stromal mast cells, a hemangiopericytoma-like vascular pattern, and calcification. Two cases showed small foci of glandular (biphasic) differentiation. Immunohistochemically, all of the seven cases were positive for epithelial membrane antigen, four of six were positive for pan-keratin, three of six were positive for S-100, two of four were positive for CD99, and six of six were negative for desmin. Clinical follow-up in six cases ranged from 8 to 48 months (median, 21 mo). Local recurrence developed in three patients at 9, 20, and 24 months, respectively. In one of these three patients, lung metastases developed at 13 months, and the patient died of disseminated disease at 23 months. In another of the three patients, lung metastases developed at 27 months. Three patients had no evidence of disease at 8, 15, and 15 months. Our data are too limited to indicate any clinical differences between myxoid synovial sarcoma and conventional synovial sarcoma Recognition of this rare histologic variant of synovial sarcoma is important because it can easily be mistaken for other myxoid spindle cell neoplasms, potentially resulting in suboptimal therapy.

Prognostic features of thyroid cancer. A long-term followup of 68 cases.

Sixty-eight cases of thyroid cancer were followed for 10 to 38 years after diagnosis. A minimum followup period of 10 years was necessary because of the long natural history of low-grade thyroid carcinoma. The prognosis of the disease was evaluated with regard to several parameters: age, sex, histologic appearance of the tumor, extent of disease, and treatment. The best prognosis was found in women less than 40 years of age with papillary carcinoma in whom there was neither extrathyroid extension nor metastasis and who were treated by surgery alone. Extrathyroidal cancer in the neck treated by radical neck dissection had a 100% survival rate at 15 years postdiagnosis. The poorest prognosis was in male patients over 60 years of age with metastatic undifferentiated carcinoma.