Novel therapeutic options for alveolar soft part sarcoma: antiangiogenic therapy, immunotherapy and beyond.

PURPOSE OF REVIEW: Alveolar soft part sarcoma (ASPS) represent 0.5% of sarcomas, defining a rarest among rare malignancies. It affects young adults, displaying slow-growing mass of the thigh, head and neck, and trunk. Although quite indolent, a majority of cases displays an advanced disease with lung bone or central nervous system metastasis. Complete surgery is the cornerstone of localized ASPS, and advanced diseases poorly respond to chemotherapy. Here discuss recent progress in molecular characterization of ASPS and future prospects of therapeutic approaches. RECENT FINDINGS: ASPS is characterized by a specific oncogenic translocation ASPSCR1-TFE3 that induce hepatocyte growth factor receptor (MET) overexpression, angiogenesis, and immunosuppression in the tumor microenvironment. These specific biological features have encouraged the successful exploration of MET inhibitors, antiangiogenic drugs, and immunotherapy. We reviewed the main tracks of ASPS biology and recent insights from targeted therapies is ASPS mainly driven tyrosine kinase inhibitors (especially antiangiogenics), immune-checkpoint inhibitors, and their combinations. SUMMARY: Overall, antiangiogenics and anti Programmed cell death 1/Programmed cell death ligand 1 therapies showed a significant activity in ASPS that warrants additional investigation through randomized trials to validate those results and through ancillary biological studies to better understand resistance mechanisms and biomarkers of response.

Magnetic Resonance Features and Characteristic Vascular Pattern of Alveolar Soft-Part Sarcoma.

OBJECTIVE: The aim of this study was to investigate the magnetic resonance (MR) features of alveolar soft-part sarcoma (ASPS). METHODS: We studied 12 patients with ASPS confirmed by pathology in this retrospective study. MR features were analyzed, especially for the location, morphology, signals, and related enhanced features of the tumor vessels. RESULTS: Flow voids were shown in the central part of the tumor on T2-weighted imaging (T2WI) in all patients; they were arrayed in a radiating mode gathered toward the center (8 cases), designated by us as vascular center-gathered syndrome (VCGS), or scattered like twigs (4 cases). The flow voids were accompanied by high signals in all patients, including tubular (6 cases) and platy (6 cases) signals. Slightly higher signals were shown in the peripheral part of the tumor in all patients. Flow voids in the peripheral part were shown in all patients, and the majority of the flow voids surrounded the tumor (8 cases). The vessels around the tumor in 9 patients showed high signals, and the majority of the vessels were located at the superior and inferior poles (8 cases). 6 patients underwent enhanced scanning, including moderate (5 cases) and significant enhancement (1 case). CONCLUSION: Low signals of radiating flow voids accompanied by high signals of slow blood flow or blood sinuses in the center part have high significance for the diagnosis of ASPS.

Crystal-deficient alveolar soft-part sarcoma with cutaneous involvement: a case report.

Alveolar soft-part sarcoma (ASPS) is a rare distinctive sarcoma, in most cases involving deep soft tissues of the extremities. It is associated with a specific unbalanced translocation, der(17)t(X;17)(p11;q25) that results in the formation of an ASPL-TFE3 fusion gene. Microscopically, it is typified by an alveolar growth of large cells containing typical periodic acid-Schiff-positive rod-shaped crystals, often serving as a diagnostic clue. Other distinctive features include nuclear immunoreactivity for transcription factor 3 (TFE3) protein and a typical ultrastructural finding of large crystals with a rectangular or rhomboid shape. The authors present an unusual case of ASPS with cutaneous involvement, which did not exhibit typical large crystals; there were striking round granules. Molecular genetic study revealed fusion transcript ASPL-TFE3, type 2. To the best of our knowledge, cutaneous involvement of a crystal-deficient ASPS has not been reported.

Alveolar soft-part sarcoma of the tongue.

Alveolar soft-part sarcoma is a rare, aggressive malignancy of uncertain histologic origin with a propensity for vascular invasion and distant metastasis. This neoplasm may mimic benign vascular neoplasms or malformations but careful evaluation of the unique imaging features on CT scans, MR images, and angiograms lead to the correct diagnosis. We present a case of alveolar soft-part sarcoma of the tongue and emphasize its radiologic and clinical features.

Highly vascular pelvic tumor causing high-output heart failure because of massive arteriovenous shunting: a case report.

A 53-year-old Japanese woman underwent investigation of her heart murmur. A continuous abdominal bruit was heard. Blood gas analysis and chest X-ray showed congestive heart failure. Enhanced computed tomography of the pelvis showed a 10 x 4 cm hypervascular tumor in the retroperitoneal space. Cardiac catheterization disclosed a cardiac output of 13.2 L/min and a step-up of oxygen at the right common iliac vein. Abdominal aortic angiography showed an extremely vascular pelvic tumor and rapid filling of the inferior vena cava. This is a rare case of a highly vascular pelvic tumor causing high-output heart failure because of th massive arteriovenous shunting.

Pulmonary metastases of alveolar soft-part sarcoma: CT findings in three patients.

Alveolar soft-part sarcoma is a rare soft tissue sarcoma of young adults with unknown histogenesis, and the organ most frequently involved in metastasis is the lung. We report the CT findings of three patients of pulmonary metastases of alveolar soft-part sarcoma, which manifested as clearly enhanced pulmonary nodules or masses. On enhanced scans, some of the masses were seen to contain dilated and tortuous intratumoral vessels.

Pulmonary Metastases of Alveolar Soft-Part Sarcoma: CT Findings in Three Patients

Alveolar soft-part sarcoma is a rare soft tissue sarcoma of young adults with unknown histogenesis, and the organ most frequently involved in metastasis is the lung. We report the CT findings of three patients of pulmonary metastases of alveolar soft-part sarcoma, which manifested as clearly enhanced pulmonary nodules or masses. On enhanced scans, some of the masses were seen to contain dilated and tortuous intratumoral vessels.

Antegrade catheterization of the brachial artery for embolizing a sarcoma of the forearm.

A case is described in which embolization of an alveolar soft part sarcoma, involving a forearm, was successfully achieved via cannulation of the brachial artery. The procedure was performed safely and more easily from this direct approach.

Clinical presentation of alveolar soft-part sarcoma.

Alveolar soft-part sarcomas are rare and seldom considered in the differential diagnosis of a soft-tissue mass. Thus, early clinical recognition can be elusive. The authors have identified several clinical and radiographic features of alveolar soft-part sarcoma, emphasizing the importance of magnetic resonance imaging in the preoperative diagnostic and staging workup. Accurate diagnosis and treatment of this unusual tumor requires clinical suspicion and clinicopathologic correlation with appropriate radiographic studies. If the clinical or radiographic interpretation is equivocal, early biopsy is essential to differentiate alveolar soft-part sarcoma from arteriovenous malformation.