ASPSCR1-TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma

Alveolar soft part sarcoma (ASPS) is a soft part malignancy affecting adolescents and young adults. ASPS is characterized by a highly integrated vascular network, and its high metastatic potential indicates the importance of ASPS’s prominent angiogenic activity. Here, we found that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance; however, it is required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 is frequently associated with super-enhancers (SEs) upon its DNA binding, and the loss of its expression induces SE-distribution dynamic modification related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identified Pdgfb, Rab27a, Sytl2, and Vwf as critical targets associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. Upregulation of Rab27a and Sytl2 promotes angiogenic factor-trafficking to facilitate ASPS vascular network construction. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via modulating the SE activity.

Alveolar soft part sarcoma of the retroperitoneum: A case report

Alveolar soft part sarcoma is a rare soft tissue tumor with uncertain histogenesis. It is a slow growing tumor with a high rate of metastasis. The tumor is not easily identified as clinical symptoms are not pronounced. The retroperitoneum is a rare location of tumor, with a few cases published in literature. Surgical excision is the mainstay of treatment. Here we describe a rare case of a large retroperitoneal Alveolar soft part sarcoma in a young female with radiological and histopathological findings.

Alveolar Soft Part Sarcoma: Progress Toward Improvement in Survival? A Population-Based Study

Background: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade.Methods: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017 were identified from the Bone and Soft-Tissue Tumor Registry in Japan. The Kaplan–Meier estimate and Cox proportional hazard model were used to investigate the survival outcomes and factors affecting prognosis.Results: The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were >25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors >5 cm (5–10 cm, 81%; >10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. The use of pazopanib significantly prolonged survival in patients who received systemic treatment (p = 0.045), whereas doxorubicin-based cytotoxic chemotherapy did not. Overall, a trend toward improved DSS for metastatic ASPS has been observed since 2012 (5-year, 58%–65%; p = 0.117), when pazopanib was approved for use in advanced disease.Conclusion: The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted drugs encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.

Imaging and Pathological Features of Alveolar Soft Part Sarcoma: Analysis of 16 Patients

Context Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor most commonly occurring in deep intramuscular plane of lower extremities of adolescents and young adults. It is a highly vascular, slow growing tumor with malignant potential having lung as the most common site of metastases at the time of presentation. Aims The aim is to review the imaging findings of ASPS and determine characteristic imaging features of this rare tumor. Materials and Methods Sixteen patients having histopathological diagnosis and preoperative imaging of ASPS attending the dedicated sarcoma clinic at our institute were included in the study. The demographic, clinical, and imaging data were retrieved from the case records and then evaluated for characteristic imaging features which may raise suspicion of ASPS. Results The patients ranged from 3 to 72 years of age and with a slight male preponderance. Of the eight CECTs evaluated, 62.5% tumors showed well-defined lobulated margins, 87.5% cases showed intense enhancement with presence of feeder vessels. On CEMRI of 10 patients, 70% had well circumscribed lobulated margins with intense enhancement and tortuous flow voids in most of them. All cases showed T2 hyperintense signal. Fourteen of 16 (87.5%) patients had metastatic disease with lung as the most common site (92.8%). Conclusion ASPS is a rare soft tissue sarcoma seen in children and young adults. Imaging may mimic a vascular malformation due to the presence of tortuous feeders. Misdiagnosis at an early stage may lead to later metastatic presentation of the disease, thus emphasizing the need to suspect it on imaging.

RADI-04. Stereotactic radiosurgery in alveolar soft part sarcoma brain metastasis

Background Alveolar soft part sarcoma (ASPS), although rare, has the highest incidence of brain metastasis amongst all sarcomas. Stereotactic radiosurgery (SRS) has been shown to be a well tolerated and effective treatment of intracranial sarcomatous metastasis. However, there is a paucity of published literature that guides radiation therapy in this condition. Methods This is a single centre retrospective review of all ASPS patients with intraparenchymal brain metastasis in our centre treated with stereotactic radiosurgery (SRS). SRS dosing is dichotomised into high and low dose (≥25 Gy and &lt;25 Gy respectively) and outcomes such as local recurrence (LR) and radiation effects are noted. Successful treatment was defined as a lesion that regressed, is stable, or has less than 25% increase in tumour volume. Local recurrence (LR) was defined as increase in tumour volume by more than 25% during follow up. Results There were three patients with 11 ASPS metastatic brain lesions, one of which underwent retreatment. Each lesion was followed up for a mean duration of 12 months (range: 5 – 22 months). Five lesions treated with a high dose regime and six lesions were given low dose. Lesions treated with high dose SRS experienced significantly less LR (20% vs 83.3%, OR 20.0 [95%CI 0.93 – 430), p = 0.036) with no increase in undue symptomatic radiation effects. Retreatment of lesions with LR after initial SRS using a low dose regime was successful, albeit only in the single recurrent lesion. Conclusions We conclude that SRS can be used as a first line treatment for ASPS brain metastasis that are not surgically accessible and that using a high dose for treatment is effective and safe. Multicentre collaborative studies can be performed to validate this claim.