Extraskeletal myxoid chondrosarcoma: Clinicopathological features and outcomes from the United States sarcoma collaborative database.

BACKGROUNDS AND OBJECTIVES: This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients. METHODS: EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed. RESULTS: Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio [HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified. CONCLUSIONS: Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset.

Relevance of the combination of external beam radiotherapy with the hypoxia-activated prodrug ICF05016 in an experimental model of extraskeletal myxoid chondrosarcoma.

Currently, there is no gold standard treatment for Extraskeletal Myxoid Chondrosarcomas (EMC) making wide margin surgical resection the most effective alternative treatment. Nevertheless, in previous preclinical studies our lab demonstrated the potential of the hypoxia-activated prodrug (HAP) ICF05016 on EMC murine model inoculated with the H-EMC-SS human cell line. The aim of this study was to assess, in vivo, the relevance of the combination of this HAP with External Beam Radiotherapy (EBR). Firstly EMC-bearing mice were treated with 6 Gy or 12 Gy of EBR (single 6 MV photon). Then for combination of HAP and EBR, animals received 6 doses of ICF05016 (46.8 µmol/kg, intravenously) at 4-day intervals, with 6 Gy EBR performed 24 h after the 3rd dose of HAP. Animals were monitored throughout the study for clinical observations (tumour growth, side effects) and survival studies were performed. From tumour samples, PCNA, Ki-67 and p21 expressions were used as markers of proliferation and cell cycle arrest. Statistical significances were determined using Kruskall-Wallis and log rank tests. The radiosensitivity of the EMC model was demonstrated at 12 Gy with significant inhibition of tumour growth. Then, the HAP strategy potentiated EBR efficacy at a lower dose (6 Gy) by improving survival without generating side effects. Thus, results of this study showed the potential interest of ICF05016 for the combination with EBR in the management of EMC.

Comprehensive guidance on the diagnosis and management of primary mesenchymal tumours of the thyroid gland.

Most primary thyroid tumours are of epithelial origin. Primary thyroid mesenchymal tumours are rare but are being increasingly detected. A vast majority of thyroid mesenchymal tumours occur between the fourth and seventh decades of life, presenting as progressively enlarging thyroid nodules that often yield non-diagnostic results or spindle cells on fine needle aspiration biopsy. Surgery is the preferred mode of treatment, with adjuvant chemoradiotherapy used for malignant thyroid mesenchymal tumours. Benign thyroid mesenchymal tumours have excellent prognosis, whereas the outcome of malignant thyroid mesenchymal tumours is variable. Each thyroid mesenchymal tumour is characterised by its unique histopathology and immunohistochemistry. Because of the rarity and aggressive nature of malignant thyroid mesenchymal tumours, a multidisciplinary team-based approach should ideally be used in the management of these tumours. Comprehensive guidelines on the management of thyroid mesenchymal tumours are currently lacking. In this Review, we provide a detailed description of thyroid mesenchymal tumours, their clinical characteristics and tumour behaviour, and provide recommendations for the optimal management of these tumours.

The Extracompartmental Tumoral Invasion of Extraskeletal Myxoid Chondrosarcoma Induces Distant Metastasis.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant soft-tissue tumor and often shows extracompartmental tumoral invasion. The aim of our study was to investigate the clinical features, especially extracompartmental tumoral invasion (ETI) of EMC. PATIENTS AND METHODS: A total of 35 operative patients diagnosed with EMC were enrolled in this study from January 1980 to March 2018 in the Cancer Institute Hospital of The Japanese Foundation for Cancer Research. The operative procedure was principally wide excision. Univariate analysis assessed how clinicopathological factors (e.g. age, gender, tumor site, tumor size, histopathological grade, surgical margin, metastasis before operation, barrier invasion, local recurrence, metastasis after operation) influenced patient prognosis. We assessed how clinicopathological factors influenced ETI of EMC. RESULTS: Among 35 patients, 10 patients showed ETI. The average follow-up was 5.57 (range=0.2-20 years). The 5- and 10-year overall survival was 91.3% and 71.2%, respectively. The 5- and 10-year overall survival of patients with M0 disease was 96.1% and 73.2%, respectively, while both were 75.0% for those with M1 disease, respectively. The patients with distant metastasis at first visit tended to have a poor prognosis (p=0.07). It is notable that all of the 10 patients with ETI had distant metastasis after surgery. CONCLUSION: Patients with distant metastasis at first visit tended to have a poor prognosis. ETI of EMC induced distant metastasis after surgery. Patients with ETI of EMC should, therefore, be carefully monitored over a prolonged period.

Extraskeletal Myxoid Chondrosarcoma of the Midfoot Presenting as Charcot Arthropathy: A Case Report.

CASE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue malignancy that very seldomly presents in the foot or ankle and as a result is not commonly in the differential of patients presenting with foot pain. We cite a case of EMC presenting in the atypical location of the midfoot. Because of its location and similarities, this tumor was initially misdiagnosed and mistreated by multiple medical providers as midfoot Charcot arthropathy. CONCLUSIONS: Neoplastic etiologies, including EMC, should remain in the differential for atypical, refractory foot pain that presents in a manner similar to Charcot foot.

Extraskeletal Myxoid Chondrosarcomas: Combined Modality Therapy With Both Radiation and Surgery Improves Local Control.

OBJECTIVE: We evaluated our experience treating patients with localized extraskeletal myxoid chondrosarcomas (EMCs) to evaluate outcomes and relapse rates in order to better inform treatment decisions for these rare soft tissue sarcomas. MATERIALS AND METHODS: We reviewed the records of 41 consecutive patients with localized EMC treated at our institution from 1990 to 2016. Most patients (n=33, 80%) received combined modality therapy with surgery and radiation therapy, whereas only 8 (20%) underwent surgery alone. The Kaplan-Meier method was used to estimate rates of overall survival, disease-specific survival, local control (LC), and distant metastatic-free survival (DMFS). RESULTS: Median follow-up time was 94 months (range, 8 to 316). The 10-year LC, DMFS, disease-specific survival, and overall survival rates were 90%, 69%, 85%, and 66%, respectively. There were 5 patients (12%) with local relapse at a median time of 75 months (range, 13 to 176). On univariate analysis, the only significant factor associated with poorer LC was the use of surgery alone (10 y LC, 63% vs. 100% for combined modality therapy, P=0.004), which remained the only factor also significant on the multivariable analysis (P=0.02; hazard ratio [HR], 12.7; 95% confidence interval [CI], 1.4-115.3). In total, 13 patients (32%) developed distant metastatic at a median time of 28 months (range, 3 to 154). Interestingly, local recurrence was the only factor associated with poorer DMFS on multivariate analysis (P=0.04; HR, 3.9; 95% CI, 1.1-14.7). CONCLUSIONS: For patients with EMC, surgery alone was associated with a higher risk of local recurrence. Therefore, we recommend optimal local therapeutic strategies upfront with both surgery and radiation therapy to reduce the risk of local and ultimately distant recurrence.

PET in the Diagnostic Management of Soft Tissue Sarcomas of Musculoskeletal Origin.

Soft tissue sarcomas (STSs) account for less than 1% of adult solid tumors and about 7% of pediatric malignancies, causing 2% of cancer-related deaths. With the advent of PET-computed tomography (CT), the value of (18) fluorine-2-fluoro-2-deoxy-d-glucose (FDG) PET imaging to improve the management of STSs has been explored. FDG PET imaging has been found useful in restaging and treatment response assessment. This article reviews current knowledge and application of FDG PET-CT in initial diagnosis, staging, restaging, treatment response monitoring, and prognosis, with a brief overview of the most common histologic subtypes of STS.

Management of Primary Soft Tissue Tumors of the Chest Wall.

Primary chest wall tumors are rare and represent a challenging clinical entity. Preoperative work-up includes a thorough history, radiographic imaging, and a biopsy approach that does not make a future definitive resection more difficult. Treatment decisions are based on tumor histology, stage, local aggressiveness, and responsiveness to chemotherapy and radiation. Wide excision is the foundation of treatment of most malignant primary chest wall tumors. The role of radiation therapy in the neoadjuvant or adjuvant setting is to reduce local recurrence. The use of adjuvant chemotherapy is more controversial. For most primary chest wall malignancies, margin-negative resection remains the best chance of cure.

Diagnosis of extraskeletal myxoid chondrosarcoma in the thigh using EWSR1-NR4A3 gene fusion: a case report.

BACKGROUND: Extraskeletal myxoid chondrosarcoma is a rare soft tissue sarcoma that has unusual ultrastructural and molecular features. However, unlike other soft tissue sarcomas, it does not have specific clinical symptoms or radiological features, which can make its diagnosis difficult. Nevertheless, extraskeletal myxoid chondrosarcoma has a rare gene fusion (EWSR1-NR4A3) that is useful for making a differential diagnosis. CASE PRESENTATION: A 43-year-old Japanese man presented with a soft tissue mass in his right thigh. A physical examination and radiography revealed a large soft tissue mass. During magnetic resonance imaging, the mass exhibited isointensity on T1-weighted images and high intensity on T2-weighted images, as well as gadolinium enhancement at the side edge of the partition structure. Thus, we considered a possible diagnosis of a malignant myxoid soft tissue tumor, such as myxoid liposarcoma, myxofibrosarcoma, or metastatic carcinomas, including myoepithelial tumor and neuroendocrine tumor, and performed an incisional biopsy to make a definitive diagnosis. The pathological findings revealed a lobulated tumor with a myxoid structure and atypical spindle-shaped cells that created eosinophilic cord-like forms. Immunohistochemistry revealed that the tumor was positive for S-100 and negative for synaptophysin, chromogranin A, and pan keratin (AE1/AE3). The percentage of Ki-67 was 10 % in the hot spot area. Based on these clinicopathological findings, we initially considered the possibility of a myxoid liposarcoma, although we did not observe any lipoblasts. Therefore, we considered the possibility of an extraskeletal myxoid chondrosarcoma. As this tumor is very rare, we searched for the EWSR1-NR4A3 gene fusion using fluorescence in situ hybridization, which confirmed the diagnosis of extraskeletal myxoid chondrosarcoma. Positron emission tomography-computed tomography did not identify any obvious metastases, and we performed radical resection of our patient's vastus medialis and femur with a 3 cm margin. After the resection, we treated his resected femur using liquid nitrogen, and reconstructed his femur using autogenous fibula and plate fixation. No local recurrence or metastasis was observed at the 1-year follow-up. CONCLUSION: Genetic testing is useful for diagnosing extraskeletal myxoid chondrosarcoma based on the presence of the EWSR1-NR4A3 gene fusion.

Immunotherapy for Bone and Soft Tissue Sarcomas.

Although multimodal therapies including surgery, chemotherapy, and radiotherapy have improved clinical outcomes of patients with bone and soft tissue sarcomas, the prognosis of patients has plateaued over these 20 years. Immunotherapies have shown the effectiveness for several types of advanced tumors. Immunotherapies, such as cytokine therapies, vaccinations, and adoptive cell transfers, have also been investigated for bone and soft tissue sarcomas. Cytokine therapies with interleukin-2 or interferons have limited efficacy because of their cytotoxicities. Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), an activator of the innate immune system, has been approved as adjuvant therapeutics in combination with conventional chemotherapy in Europe, which has improved the 5-year overall survival of patients. Vaccinations and transfer of T cells transduced to express chimeric antigen receptors have shown some efficacy for sarcomas. Ipilimumab and nivolumab are monoclonal antibodies designed to inhibit immune checkpoint mechanisms. These antibodies have recently been shown to be effective for patients with melanoma and also investigated for patients with sarcomas. In this review, we provide an overview of various trials of immunotherapies for bone and soft tissue sarcomas, and discuss their potential as adjuvant therapies in combination with conventional therapies.

Submucosal neoplasms of the laryngeal introitus.

BACKGROUND: The differential diagnosis of endolaryngeal mesenchymal neoplasms includes a wide spectrum of benign and malignant pathologies, which have been rarely photo-documented and assessed as a group. METHODS: Non-epithelial neoplasms of the endolarynx seen at our centre from 2002 to 2011 (n = 38; 36 treated at our institution) were retrospectively reviewed, with attention to clinical presentation, radiographic imaging, operative management, histology, and pre- and post-operative endoscopy. Submucosal squamous cell carcinomas, mucosal cysts, amyloid and Teflon granulomas were excluded. RESULTS: Twenty-three of a total of 36 patients underwent definitive endoscopic surgical treatment. Supraglottic pathologies included lymphoma, lipoma, neuroendocrine carcinoma, lymphangioma, oncocytoma, haemangioma, synovial cell sarcoma and benign spindle cell neoplasm. Transglottic pathologies included synovial cell sarcoma and granular cell tumour. Glottic pathologies included granular cell tumour, osteoma, rhabdomyoma, rhabdomycosarcoma and myofibroblastic sarcoma. Subglottic pathologies included chondrosarcoma, neurofibroma, adenoid cystic carcinoma and vascular malformation. CONCLUSION: The site of origin, degree of malignant behaviour and sensitivity to adjuvant treatment determined the course of surgical management, i.e. endolaryngeal versus transcervical, and limited removal versus wider resection.

Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum.

PEComas (tumors showing perivascular epithelioid cell differentiation) are a family of mesenchymal neoplasms that include angiomyolipoma, clear cell "sugar" tumor of the lung, lymphangiomyomatosis, and a group of uncommon lesions that arise in soft tissue, visceral organs, and skin. We describe a distinctive variant of PEComa that shows extensive stromal hyalinization, a feature not previously described in these tumors. Thirteen PEComas with extensive stromal hyalinization were identified from a total of 70 cases of PEComa received between 1996 and 2006 (19%). All patients were women, with a mean age of 49 years (range, 34 to 73y). One patient had tuberous sclerosis. Ten tumors (77%) arose in the retroperitoneum (8 pararenal), and 1 each in the pelvis, uterus, and abdominal wall. Median tumor size was 9.5 cm (range, 4.5 to 28 cm). All except 2 were grossly well-circumscribed. The tumors were composed of cords and trabeculae of cytologically uniform bland epithelioid cells with palely eosinophilic, granular to clear cytoplasm and round nuclei with small nucleoli, embedded in abundant densely sclerotic stroma. Five tumors contained a spindle cell component, and 6 showed focally sheetlike areas. In all cases the tumor cells were focally arranged around blood vessels. All tumors lacked the delicate nesting vascular pattern typical of other PEComas. Mitoses ranged from 0 to 3/50 high-power field (mean 1) in all cases except 1. One tumor showed abrupt transition to areas with strikingly pleomorphic morphology, marked nuclear atypia, frequent mitoses (22/10 high-power field), and fascicular and nested architecture. This was the only case with necrosis. All tumors were immunopositive for desmin (usually diffusely) and HMB-45 (generally in scattered cells); 12/13 (92%) expressed smooth muscle actin, 11/12 (92%) caldesmon, 11/12 (92%) microphthalmia transcription factor (D5), and 3/13 (23%) melan-A. Only 1 (8%) was focally S-100 positive. All tumors were negative for epithelial membrane antigen, PAN-K, and KIT (CD117). Follow-up was available for 9 patients, ranging from 10 to 64 months (median, 33). One patient (whose tumor showed transition to high-grade malignant morphology) developed metastases to lung, liver, and abdominal wall. No other tumor has recurred or metastasized thus far. Sclerosing PEComa is a distinctive variant with a predilection for the pararenal retroperitoneum of middle-aged women. Sclerosing PEComas seem to pursue an indolent clinical course, unless associated with a frankly malignant component. Long-term follow-up will be required to confirm these findings.

Genetics for the diagnosis and treatment of mesenchymal tumors.

Cytogenetics and molecular genetics play an important role in the diagnosis of soft tissue and bone mesenchymal tumors. This update focuses on cytogenetic and molecular genetic techniques commonly used for evaluation of mesenchymal tumors, including karyotyping, fluorescent in situ hybridization, and polymerase chain reaction. Examples of different techniques, inherent technical problems, and interpretation of the results are discussed. Additionally, limitations related to the type of material available for genotyping (fresh, frozen, or formalin-fixed paraffin-embedded tissue) are covered. Cytogenetic and molecular genetic alterations identified in various mesenchymal tumors are often valuable for diagnosis, prognosis, and treatment strategies.

[Autotransplantation for solid tumors]. / Autotransplantacja w guzach litych.

Over the last three decades, there have been a number of advances made in the treatment of haematological malignancies including an increasingly defined role in curative therapy programmes for high dose chemotherapy (HDC) with stem cell support. This has provided an impetus for similar approaches to be tested in solid tumours. Drug resistance is one of the most important reasons for treatment failure in these diseases, and therefore attempting to overcome it with HDC is an obvious strategy to investigate. This rationale is supported by laboratory data demonstrating that dose correlates with number of cells killed, and that increasing drug doses by 5-10 fold can overcome resistance. Clear evidence of a dose-response effect in patients is provided by numerous clinical trials of chemotherapy in solid tumours. A large number of studies have investigated HDC in solid tumours, particularly in those malignancies which demonstrate initial chemo-sensitivity, but later relapse. Except for breast cancer, for other solid tumours there are no randomised trials defining the role of HDC. Many of the trials are small pilot studies in heavily pretreated patients with large volume disease and therefore any conclusions must be guarded.

Treatment options for orthopaedic oncologic entities.

Over the past 2 decades, tremendous advancement in the understanding of tumor natural history and treatment has occurred. If the basic principles are followed, the evaluation and appropriate treatment of musculoskeletal tumors can be reproduced successfully by any conscientious surgeon. Many benign bone and soft-tissue tumors can and probably should be treated by the community orthopaedic surgeon, and this chapter is biased toward treatment of those lesions. The encounter of a malignant lesion is probably beyond the scope of practice of most practicing orthopaedic surgeons. The assessment of the patient and treatments rendered in the first meetings may well dictate the ultimate outcome of survival and limb preservation: thus, patients with such lesions should be treated by experienced orthopaedic oncologists. With the small numbers of these lesions and the extreme consequences of mishandling them, it would be imprudent to do otherwise.