Alveolar Soft Part Sarcoma

Cancer MONDO:0011655 Pathograph 15 Show in embeddings browser soft tissue sarcoma

Alveolar soft part sarcoma is a rare translocation-driven soft tissue sarcoma that most often affects adolescents and young adults. It commonly arises as a deep soft tissue mass of the extremities and is characterized by an ASPSCR1-TFE3 fusion, strong angiogenic biology, and a tendency toward delayed pulmonary and brain metastases.

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5
Pathophys.
2
Histopath.
4
Phenotypes
15
Pathograph
2
Genes
6
Medical Actions
4
Differentials
2
Datasets
4
Trials
2
Models
1
Deep Research
⚙

Pathophysiology

5
ASPSCR1-TFE3 Fusion Oncogene
A characteristic unbalanced der(17)t(X;17)(p11;q25) translocation fuses ASPSCR1 to TFE3, creating an aberrant transcription factor that redirects gene expression programs in tumor cells.
mesenchymal cell CL:0008019 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves mesenchymal cell (CL:0008019). CL:0008019 is a cell type from the Cell Ontology.
ASPSCR1 hgnc:13825 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves ASPSCR1 (hgnc:13825). hgnc:13825 is a gene from the HUGO Gene Nomenclature Committee. TFE3 hgnc:11752 HUGO Gene Nomenclature Committee (hgnc) Relation: this pathophysiological event involves this gene This pathophysiological event involves TFE3 (hgnc:11752). hgnc:11752 is a gene from the HUGO Gene Nomenclature Committee.
positive regulation of transcription by RNA polymerase II GO:0045944 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal positive regulation of transcription by RNA polymerase II (GO:0045944). GO:0045944 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Experimental models
ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines CELL LINE Models fusion-dependent transcriptional and chromatin regulation.
Downstream
Angiogenic Tumor Program Aberrant transcriptional activity promotes angiogenic tumor biology
Mitochondrial Biology Program ASPSCR1-TFE3 transcriptional programs include mitochondrial biology.
Cyclin D1-CDK4 Cell-Cycle Dependency ASPSCR1-TFE3 transcriptional programs drive cyclin D1/CDK4-dependent proliferation
Show evidence (2 references)
PMID:37626447 SUPPORT Other
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly supports the recurrent translocation and ASPSCR1-TFE3 fusion as defining disease biology.
PMID:38657118 SUPPORT In Vitro
"Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion."
The mechanistic study abstract supports ASPSCR1::TFE3 as the oncogenic driver fusion.
Angiogenic Tumor Program
Alveolar soft part sarcoma is typically highly vascular, with expression of angiogenic programs that support tumor growth and provide the rationale for antiangiogenic systemic therapies.
endothelial cell CL:0000115 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves endothelial cell (CL:0000115). CL:0000115 is a cell type from the Cell Ontology.
angiogenesis GO:0001525 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased angiogenesis (GO:0001525). GO:0001525 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Metastatic Progression Prominent angiogenic activity supports hematogenous metastatic progression.
Show evidence (3 references)
PMID:38657118 SUPPORT In Vitro
"identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology."
The mechanistic study directly links ASPSCR1::TFE3 to angiogenesis and cell-proliferation transcriptional programs.
PMID:37029109 SUPPORT Model Organism
"ASPSCR1::TFE3 thus orchestrates higher ordered angiogenesis via modulating the SE activity."
Epigenomic perturbation and in-vivo experiments establish a direct fusion-driven angiogenic program.
PMID:37987424 SUPPORT Human Clinical
"Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3)."
The imaging cohort supports the highly vascular tumor phenotype in patients.
Mitochondrial Biology Program
ASPSCR1-TFE3 regulates mitochondrial biology and mitochondrial biogenesis as part of the core oncogenic transcriptional program.
mitochondrion organization GO:0007005 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal mitochondrion organization (GO:0007005). GO:0007005 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (2 references)
PMID:38657118 SUPPORT In Vitro
"identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology."
The mechanistic study identifies mitochondrial biology as a core ASPSCR1::TFE3 transcriptional program.
PMID:38657118 SUPPORT In Vitro
"The ASPSCR1::TFE3 fusion propels the growth of alveolar soft part sarcoma by activating transcriptional programs that regulate proliferation, angiogenesis, mitochondrial biogenesis, and differentiation and can be therapeutically targeted to improve treatment."
The paper's significance statement supports mitochondrial biogenesis as an activated ASPS transcriptional program.
Cyclin D1-CDK4 Cell-Cycle Dependency
Recent preclinical work shows that ASPSCR1-TFE3-driven transcriptional programs create a cyclin D1/CDK4-dependent proliferation state that may be targetable with CDK4/6 inhibition, especially in combination with angiogenesis inhibition.
cell cycle G1/S phase transition GO:0044843 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell cycle G1/S phase transition (GO:0044843). GO:0044843 is a biological process from the Gene Ontology. ↑ INCREASED cell population proliferation GO:0008283 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell population proliferation (GO:0008283). GO:0008283 is a biological process from the Gene Ontology. ↑ INCREASED
Experimental models
ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines CELL LINE Models loss of proliferative capacity after cyclin D1/CDK4 disruption.
Downstream
Deep Soft Tissue Mass Proliferative tumor-cell outgrowth produces the characteristic slow-growing deep soft tissue mass.
Show evidence (2 references)
PMID:38657118 SUPPORT In Vitro
"cell proliferation was driven by high levels of cyclin D1 expression."
This directly supports cyclin D1 as a cell-cycle effector of ASPS proliferation.
PMID:38657118 SUPPORT Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
The xenograft result supports combined CDK4/6 and angiogenesis inhibition as a preclinical therapeutic vulnerability.
Metastatic Progression
Alveolar soft part sarcoma often follows an indolent primary course but can metastasize to the lungs, brain, bone, and other sites, sometimes years after initial diagnosis.
cell population proliferation GO:0008283 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased cell population proliferation (GO:0008283). GO:0008283 is a biological process from the Gene Ontology. ↑ INCREASED
Downstream
Pulmonary Metastases Hematogenous metastatic progression commonly seeds the lungs.
Brain Metastases Systemic dissemination can involve the central nervous system.
Bone Metastases Systemic dissemination can involve skeletal sites.
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course."
Population registry data support the combination of indolent course and frequent lung/brain metastasis.
PMID:40171452 SUPPORT Human Clinical
"Alveolar soft part sarcoma (ASPS) is a rare, indolent soft tissue sarcoma, with a high predilection for systemic dissemination."
A real-world clinical cohort supports the systemic dissemination tendency.
✶

Histopathology

2
Pseudoalveolar Organoid Architecture
Tumors have nests or organoid groups of polygonal cells separated by delicate sinusoidal vasculature, producing the classic pseudoalveolar pattern.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"The tumour cells within the nodules were arranged as organoid or glandular vesicle-like structures with abundant blood sinuses between vesicles"
The pathology cohort directly describes the characteristic nested, pseudoalveolar architecture and sinusoidal vasculature.
PAS-Positive Diastase-Resistant Cytoplasmic Crystals
Periodic acid-Schiff-positive, diastase-resistant rod- or bar-shaped cytoplasmic crystals are characteristic and help distinguish ASPS from morphologic mimics, although they are not present in every tumor.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"The tumour cells in 20 patients were PAS positive and contained rod-shaped crystals in the cytoplasm"
PAS-positive rod-shaped crystals were observed in 20 of 26 tumors in the pathology cohort.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Alveolar Soft Part Sarcoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

4
Neoplasm 2
Deep Soft Tissue Mass Soft tissue neoplasm HP:0031459 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Deep soft tissue mass, annotated with Soft tissue neoplasm (HP:0031459). HP:0031459 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:38291475 SUPPORT Human Clinical
"The clinical symptoms mainly included painless enlarged masses in deep soft tissues."
The clinicopathologic cohort directly supports a painless deep soft tissue mass presentation.
PMID:37987424 SUPPORT Human Clinical
"all tumors were deeply seated."
The imaging cohort supports the deep location and large mass-like presentation.
Pulmonary Metastases Neoplasm of the lung HP:0100526 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Neoplasm of the lung (HP:0100526). HP:0100526 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"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%)."
The national registry cohort directly supports lung metastasis during the disease course after localized ASPS.
PMID:40171452 SUPPORT Human Clinical
"The most common site of primary was the extremities (73%), and the most common sites of metastasis included the lungs (82%) and bones (21%)."
A contemporary real-world cohort also identifies lung as the most common metastatic site.
Other 2
Brain Metastases Neoplasm of the central nervous system HP:0100006 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Neoplasm of the central nervous system (HP:0100006). HP:0100006 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40171452 SUPPORT Human Clinical
"Brain metastasis was seen in 7 patients at baseline (25.9%)."
The real-world cohort supports brain metastasis as a notable ASPS complication.
PMID:40171452 SUPPORT Human Clinical
"Patients with brain metastasis were seen to have markedly poor outcomes."
The same cohort supports clinical severity of brain metastasis in ASPS.
Bone Metastases Neoplasm of the skeletal system HP:0010622 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bone metastases, annotated with Neoplasm of the skeletal system (HP:0010622). HP:0010622 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"bone, n = 12"
The national registry cohort reports bone metastases in 14% of metastatic ASPS patients.
PMID:40171452 SUPPORT Human Clinical
"The most common site of primary was the extremities (73%), and the most common sites of metastasis included the lungs (82%) and bones (21%)."
A contemporary real-world cohort reports bones as a common metastatic site.
🧬

Genetic Associations

2
ASPSCR1-TFE3 Fusion - ASPSCR1 Partner
Gene: ASPSCR1 hgnc:13825 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is ASPSCR1 (hgnc:13825). hgnc:13825 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (1 reference)
PMID:37626447 SUPPORT Other
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly names ASPSCR1 as one partner in the defining ASPS fusion.
ASPSCR1-TFE3 Fusion - TFE3 Partner
Gene: TFE3 hgnc:11752 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is TFE3 (hgnc:11752). hgnc:11752 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SOMATIC_DRIVER variant_origin: SOMATIC
Show evidence (1 reference)
PMID:37626447 SUPPORT Other
"The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion."
The review abstract directly names TFE3 as one partner in the defining ASPS fusion.
💊

Medical Actions

6
Complete Surgical Resection
Action: surgical excisionNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is surgical excision, annotated with Excision (NCIT:C15232). NCIT:C15232 is a clinical intervention from the NCI Thesaurus. Ontology label: Excision NCIT:C15232
Complete resection with negative margins is the preferred local therapy when disease is localized and technically resectable.
Show evidence (1 reference)
PMID:37626447 SUPPORT Other
"Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours."
The review abstract directly supports complete surgical resection as the standard local treatment strategy.
Radiation Therapy
Action: Radiation TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Radiation Therapy (NCIT:C15313). NCIT:C15313 is a clinical intervention from the NCI Thesaurus. NCIT:C15313
Radiation therapy can be used when surgical margins are inadequate or when tumors are unresectable.
Show evidence (1 reference)
PMID:37626447 SUPPORT Other
"Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours."
The same review abstract supports radiation therapy for inadequate margins or unresectable disease.
Antiangiogenic Targeted Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: pazopanib CHEBI:71219 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses pazopanib (CHEBI:71219). CHEBI:71219 is a therapeutic agent from Chemical Entities of Biological Interest. sunitinib CHEBI:38940 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sunitinib (CHEBI:38940). CHEBI:38940 is a therapeutic agent from Chemical Entities of Biological Interest. cediranib Relation: this treatment uses this therapeutic agent This treatment uses cediranib.
Antiangiogenic tyrosine kinase inhibitors, including pazopanib, sunitinib, and cediranib, have clinical activity in advanced ASPS and align with the tumor's angiogenic transcriptional program.
Mechanism Target:
INHIBITS Angiogenic Tumor Program — Antiangiogenic kinase inhibitors target vascular signaling that supports tumor growth.
Show evidence (1 reference)
PMID:31160249 SUPPORT Human Clinical
"our finding of significant clinical activity with cediranib in this disease is an important step towards the goal of long-term disease control for these young patients."
The randomized placebo-controlled trial supports clinical inhibition of the angiogenesis-dependent tumor program by cediranib.
Show evidence (3 references)
PMID:37626447 SUPPORT Other
"Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies."
The review abstract supports tyrosine kinase inhibitors as an active systemic treatment class in ASPS.
PMID:35971085 SUPPORT Human Clinical
"Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy."
Registry data support pazopanib-associated prolonged survival in metastatic ASPS.
PMID:31160249 SUPPORT Human Clinical
"Median percentage change in sum of target marker lesion diameters for the evaluable population was -8·3% (IQR -26·5 to 5·9) with cediranib versus 13·4% (IQR 1·1 to 21·3) with placebo (one-sided p=0·0010)."
The randomized placebo-controlled phase 2 trial provides direct evidence of cediranib antitumor activity despite the intrinsically indolent course of ASPS.
Atezolizumab
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: Atezolizumab NCIT:C106250 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses Atezolizumab (NCIT:C106250). NCIT:C106250 is a therapeutic agent from the NCI Thesaurus.
Anti-PD-L1 immune checkpoint inhibitor pharmacotherapy is an important systemic option for advanced ASPS, with prospective evidence for atezolizumab.
Show evidence (2 references)
PMID:37672694 SUPPORT Human Clinical
"An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses."
The prospective phase 2 study supports atezolizumab activity in advanced ASPS.
PMID:37672694 SUPPORT Human Clinical
"Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS."
The study conclusion supports immune checkpoint blockade as an effective systemic option in a subset of advanced ASPS patients.
Axitinib Plus Pembrolizumab
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: axitinib CHEBI:66910 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses axitinib (CHEBI:66910). CHEBI:66910 is a therapeutic agent from Chemical Entities of Biological Interest. pembrolizumab NCIT:C106432 NCI Thesaurus (NCIT) Relation: this treatment uses this therapeutic agent This treatment uses pembrolizumab (NCIT:C106432). NCIT:C106432 is a therapeutic agent from the NCI Thesaurus.
Combined VEGFR tyrosine-kinase inhibition and PD-1 checkpoint blockade has prospective phase 2 activity in advanced ASPS but remains an investigational combination requiring randomized evaluation.
Mechanism Target:
INHIBITS Angiogenic Tumor Program — Axitinib inhibits VEGF-receptor signaling while pembrolizumab relieves PD-1-mediated immune suppression.
Show evidence (1 reference)
PMID:31078463 SUPPORT Other
"VEGF promotes an immunosuppressive microenvironment and contributes to immune checkpoint inhibitor resistance in cancer."
This supplies the combination's angiogenesis/immune rationale; the trial did not isolate the contribution of either drug.
Show evidence (1 reference)
PMID:31078463 SUPPORT Human Clinical
"For patients with ASPS, 3-month progression-free survival was 72·7% (95% CI 37·1-90·3)."
The ASPS subgroup result directly supports prospective activity of the combination while its single-arm design limits comparative inference.
Investigational Combined CDK4/6 and Angiogenesis Inhibition
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: palbociclib CHEBI:85993 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses palbociclib (CHEBI:85993). CHEBI:85993 is a therapeutic agent from Chemical Entities of Biological Interest. sunitinib CHEBI:38940 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses sunitinib (CHEBI:38940). CHEBI:38940 is a therapeutic agent from Chemical Entities of Biological Interest.
Preclinical ASPS models support combining CDK4/6 inhibition with antiangiogenic inhibition. This strategy halted xenograft growth, but no clinical efficacy or safety inference can yet be made.
Mechanism Target:
INHIBITS Cyclin D1-CDK4 Cell-Cycle Dependency — Palbociclib inhibits CDK4/6-dependent tumor-cell proliferation.
Show evidence (1 reference)
PMID:38657118 SUPPORT In Vitro
"Disruption of cyclin D1/CDK4 signaling led to a loss of ASPS proliferative capacity"
Functional disruption directly supports the CDK4/6 dependency targeted by palbociclib.
INHIBITS Angiogenic Tumor Program — Antiangiogenic kinase inhibition targets the complementary vascular dependency.
Show evidence (1 reference)
PMID:38657118 SUPPORT Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
The xenograft result directly supports joint inhibition of the cell-cycle and angiogenic programs.
Show evidence (1 reference)
PMID:38657118 SUPPORT Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
This directly supports the class-level preclinical combination strategy; it does not establish benefit in patients.
🔬

Biochemical Markers

1
TFE3 Nuclear Immunoreactivity
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients."
The clinicopathologic cohort directly supports TFE3 protein positivity and rearrangement testing as diagnostic features.
🔬

Diagnosis

2
TFE3 Immunohistochemistry
Nuclear TFE3 immunoreactivity supports ASPS in the correct morphologic context, but it is not fully specific and molecular confirmation is more sensitive and specific.
immunohistochemical test NCIT:C51944 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:26516944 SUPPORT Other
"This translocation is diagnostically useful because the tumor nuclei are positive for TFE3 by immunohistochemistry."
The pathology review supports nuclear TFE3 immunoreactivity as a useful diagnostic marker.
ASPSCR1-TFE3 Fusion Transcript Testing
Molecular detection of the defining ASPSCR1-TFE3 fusion by RT-PCR, RNA sequencing, or complementary rearrangement testing confirms the diagnosis when morphology and TFE3 immunohistochemistry suggest ASPS.
reverse transcriptase-polymerase chain reaction NCIT:C19770 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:26516944 SUPPORT Other
"Real-time polymerase chain reaction to detect the ASPSCR1-TFE3 fusion transcript on paraffin-embedded tissue blocks has been shown to be more sensitive and specific than detection of TFE3 by immunohistochemical stain."
This directly supports fusion-transcript testing and its diagnostic advantage over TFE3 immunohistochemistry alone.
🩻

Imaging Findings

1
Hypervascular Deep Soft-Tissue Mass
MRI commonly shows a deeply seated mass with high T2 signal, numerous flow voids, high internal vascularization, and large peritumoral feeding vessels. The finding is characteristic but not disease-specific and can mimic a vascular lesion.
Mri Focal
hypervascular deep soft-tissue mass with flow voids and feeding vessels
Show evidence (1 reference)
PMID:37987424 SUPPORT Human Clinical
"the hallmark of ASPS imaging at presentation are the following characteristics: deep location, a slight hyperintense MRI SI on T1-WI and a hyperintense SI on T2-WI, numerous MRI flow voids, high internal vascularization, and large peritumoral feeding vessels."
The imaging cohort and literature review directly define the characteristic MRI appearance.
📈

Progression

2
Indolent primary growth with persistent metastatic risk
Age: Adolescence through adulthood
ASPS often progresses slowly, but localized disease retains a substantial long-term risk of distant spread. In a national registry cohort, 45% of localized cases later developed distant metastases, predominantly in lung.
Show evidence (1 reference)
PMID:35971085 SUPPORT Human Clinical
"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%)."
The population registry directly quantifies later metastatic progression after localized presentation.
Prognostic separation by metastatic status
Five-year disease-specific survival is substantially better for localized than metastatic disease; the national registry identified metastasis at presentation as the only adverse prognostic factor for disease-specific survival.
Show evidence (2 references)
PMID:35971085 SUPPORT Human Clinical
"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)."
The registry directly reports stage-stratified five-year disease-specific survival.
PMID:35971085 SUPPORT Human Clinical
"Metastasis at presentation was the only adverse prognostic factor for DSS"
The registry identifies metastatic presentation as its only adverse disease-specific-survival factor without overextending that result to other cohorts.
📊

Prevalence

1
Worldwide
Annual Incidence 0.01 per 100,000 <1 in 1,000,000
Review-level epidemiology estimates approximately one new diagnosis per 10 million people per year and 0.2-0.9% of all soft-tissue sarcomas. This is an incidence estimate, not a measured point prevalence.
Show evidence (1 reference)
url:https://www.ebi.ac.uk/europepmc/webservices/rest/PMC10632598/fullTextXML SUPPORT Other
"ASPS is an ultra-rare sarcoma with an incidence rate of only one diagnosis per 10 million population per year, accounting for 0.2–0.9% of all soft-tissue sarcomas"
The open-access review directly supplies the annual incidence and soft-tissue-sarcoma proportion; 1 per 10 million converts to 0.01 per 100,000 per year.
🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Alveolar Soft Part Sarcoma:

Paraganglioma
Overlapping Features Paraganglioma can share nested, highly vascular morphology with ASPS.
Distinguishing Features
  • Neuroendocrine-marker expression, including NSE, CgA, and synaptophysin, favors paraganglioma over ASPS.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"positivity for neuroendocrine markers such as NSE, CgA and Syn but not MyoD1, Des or others"
The pathology review provides the neuroendocrine immunophenotypic distinction from ASPS.
Alveolar Rhabdomyosarcoma
Overlapping Features Alveolar rhabdomyosarcoma can mimic pseudoalveolar architecture, especially in children and adolescents.
Distinguishing Features
  • Nuclear MyoD1 and other myogenic-marker expression favor alveolar rhabdomyosarcoma over ASPS.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"Immunohistochemical findings for alveolar rhabdomyosarcoma include the following: tumour cells expressing myogenic markers such as Des and MyoD1, with MyoD1 observable in the nucleus"
Nuclear myogenic-marker expression distinguishes alveolar rhabdomyosarcoma from ASPS.
Metastatic Clear Cell Renal Cell Carcinoma
Overlapping Features Metastatic clear cell renal cell carcinoma, including TFE3-rearranged renal carcinoma, may resemble ASPS morphologically and immunohistochemically.
Distinguishing Features
  • A renal primary and expression of epithelial, CD10, and RCC markers favor metastatic renal cell carcinoma.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"renal cell carcinomas with the ASPSCR1::TFE3 fusion also express CK and EMA epithelial markers and are positive for CD10 and RCC."
The epithelial and renal-marker profile distinguishes renal carcinoma from ASPS.
Perivascular Epithelioid Cell Tumor
Overlapping Features PEComa may have organoid perivascular growth and can itself harbor TFE3 rearrangements.
Distinguishing Features
  • A TFE3 rearrangement alone does not exclude PEComa; identification of a non-ASPS fusion partner favors PEComa.
Show evidence (1 reference)
PMID:38291475 SUPPORT Human Clinical
"Recent studies have revealed the presence of TFE3 gene rearrangements in 23% of PEComas, which involve the formation of gene fusions such as SFPQ/PSF::TFE3 and DVL2::TFE3."
The pathology review supplies a clean, complete sentence showing that TFE3 rearrangement occurs in PEComa and identifies alternative partners.
📊

Related Datasets

2
ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs geo:GSE235739
This SuperSeries is composed of the SubSeries listed below. Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology.
human MULTI OMICS n=62
PMID:38657118
Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
ASPSCR1-TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma I geo:GSE186789
Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis.
MICROARRAY n=27
PMID:37029109
Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
🔬

Clinical Trials

4
NCT03141684 PHASE_II
Phase 2 trial of atezolizumab alone or atezolizumab plus bevacizumab for advanced unresectable ASPS.
Show evidence (1 reference)
clinicaltrials:NCT03141684 SUPPORT Human Clinical
"This phase II trial studies how well atezolizumab or atezolizumab plus bevacizumab works in treating patients with alveolar soft part sarcoma that has not been treated, has spread from where it started to other places in the body (advanced) and cannot be removed by surgery (unresectable)."
ClinicalTrials.gov directly supports the atezolizumab plus/minus bevacizumab trial in advanced unresectable ASPS.
NCT02636725 PHASE_II
Phase 2 trial of combined axitinib and pembrolizumab in advanced ASPS and other soft tissue sarcomas.
Show evidence (1 reference)
clinicaltrials:NCT02636725 SUPPORT Human Clinical
"The purpose of this research study is to test if Axitinib together with Pembrolizumab can slow tumor growth and know the side effects of the combination treatment."
ClinicalTrials.gov directly supports investigation of combined axitinib and pembrolizumab.
NCT01391962 PHASE_II
Randomized phase 2 trial of cediranib versus sunitinib monotherapy with crossover at progression in metastatic ASPS.
Show evidence (1 reference)
clinicaltrials:NCT01391962 SUPPORT Human Clinical
"Determine the objective response rate (ORR) of single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS."
ClinicalTrials.gov directly supports this VEGFR TKI comparison trial in advanced ASPS.
NCT01337401 PHASE_II
International randomized double-blind placebo-controlled phase 2 CASPS trial of cediranib in metastatic ASPS, subsequently reported in the peer-reviewed randomized trial publication.
Show evidence (1 reference)
clinicaltrials:NCT01337401 SUPPORT Human Clinical
"The study is a two-arm, randomised, double-blind, international, multi-centre phase II trial of cediranib in Alveolar Soft Part Sarcoma (ASPS)."
ClinicalTrials.gov directly supports the CASPS design and disease scope.
🧫

Experimental Models

1
ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines CELL_LINE
Human ASPS tumor-cell lines and fusion perturbation systems model the transcriptional, chromatin, proliferative, angiogenic, and mitochondrial programs controlled by ASPSCR1::TFE3. Cell culture cannot reproduce the integrated human tumor microenvironment or establish clinical efficacy.
ASPSCR1::TFE3 expression or disruption cyclin D1/CDK4 pathway disruption
Organism
human NCBITaxon:9606 NCBI Taxonomy (NCBITaxon) Relation: this experimental model is built in this organism This experimental model is built in human, annotated with Homo sapiens (NCBITaxon:9606). NCBITaxon:9606 is an organism from the NCBI Taxonomy.
Cell source
Human ASPS tumor-derived cell lines
Culture
Monolayer cell culture with genetic and pharmacologic perturbation
Publication
PMID:38657118
Pathograph links
ASPSCR1-TFE3 Fusion Oncogene Models fusion-dependent transcriptional and chromatin regulation.
Show evidence (1 reference)
PMID:38657118 SUPPORT In Vitro
"ASPSCR1::TFE3 directly interacted with key epigenetic regulators at enhancers and promoters to support ASPS-associated transcription."
The cell-based mechanistic study directly supports fusion-dependent transcriptional regulation.
Cyclin D1-CDK4 Cell-Cycle Dependency Models loss of proliferative capacity after cyclin D1/CDK4 disruption.
Show evidence (1 reference)
PMID:38657118 SUPPORT In Vitro
"Disruption of cyclin D1/CDK4 signaling led to a loss of ASPS proliferative capacity"
Functional perturbation directly supports the modeled cell-cycle dependency.
Show evidence (1 reference)
PMID:38657118 SUPPORT In Vitro
"we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models"
The publication directly documents use of preclinical models to map ASPS transcriptional and chromatin biology.
🐁

Animal Models

1
ASPS tumor xenograft and patient-derived xenograft models Mus musculus
Mouse xenograft models carrying ASPSCR1::TFE3-positive ASPS were used to test fusion-dependent tumor biology and combined CDK4/6 and angiogenesis inhibition. They model tumor growth and drug response but do not establish efficacy or safety in patients.
Angiogenesis-dependent tumor development Cyclin D1-CDK4-dependent proliferation Tumor-growth arrest with combined CDK4/6 and angiogenesis inhibition
Species
Mus musculus
Genotype
ASPS tumor xenograft and patient-derived xenograft models
Genes
ASPSCR1 hgnc:13825 HUGO Gene Nomenclature Committee (hgnc) Relation: this experimental model concerns this gene This experimental model concerns ASPSCR1 (hgnc:13825). hgnc:13825 is a gene from the HUGO Gene Nomenclature Committee. TFE3 hgnc:11752 HUGO Gene Nomenclature Committee (hgnc) Relation: this experimental model concerns this gene This experimental model concerns TFE3 (hgnc:11752). hgnc:11752 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (1 reference)
PMID:38657118 SUPPORT Model Organism
"combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts."
The xenograft experiment directly supports the model's combination-drug response while remaining preclinical.
{ }

Source YAML

click to show 
name: Alveolar Soft Part Sarcoma
creation_date: "2026-05-09T14:04:43Z"
category: Cancer
categories:
- Sarcoma
- Soft Tissue Sarcoma
- Rare Cancer
parents:
- soft tissue sarcoma
disease_term:
  preferred_term: alveolar soft part sarcoma
  term:
    id: MONDO:0011655
    label: alveolar soft part sarcoma
description: >-
  Alveolar soft part sarcoma is a rare translocation-driven soft tissue sarcoma
  that most often affects adolescents and young adults. It commonly arises as a
  deep soft tissue mass of the extremities and is characterized by an
  ASPSCR1-TFE3 fusion, strong angiogenic biology, and a tendency toward delayed
  pulmonary and brain metastases.
synonyms:
- ASPS
- alveolar soft-part sarcoma
- alveolar soft tissue sarcoma
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: BELOW_1_IN_1000000
  rate_per_100000: 0.01
  notes: >-
    Review-level epidemiology estimates approximately one new diagnosis per 10
    million people per year and 0.2-0.9% of all soft-tissue sarcomas. This is an
    incidence estimate, not a measured point prevalence.
  evidence:
  - reference: url:https://www.ebi.ac.uk/europepmc/webservices/rest/PMC10632598/fullTextXML
    reference_title: "Abstract"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      ASPS is an ultra-rare sarcoma with an incidence rate of only one diagnosis
      per 10 million population per year, accounting for 0.2–0.9% of all
      soft-tissue sarcomas
    explanation: >-
      The open-access review directly supplies the annual incidence and
      soft-tissue-sarcoma proportion; 1 per 10 million converts to 0.01 per
      100,000 per year.
pathophysiology:
- name: ASPSCR1-TFE3 Fusion Oncogene
  biological_scale: MOLECULAR
  description: >-
    A characteristic unbalanced der(17)t(X;17)(p11;q25) translocation fuses
    ASPSCR1 to TFE3, creating an aberrant transcription factor that redirects
    gene expression programs in tumor cells.
  genes:
  - preferred_term: ASPSCR1
    term:
      id: hgnc:13825
      label: ASPSCR1
  - preferred_term: TFE3
    term:
      id: hgnc:11752
      label: TFE3
  cell_types:
  - preferred_term: mesenchymal cell
    term:
      id: CL:0008019
      label: mesenchymal cell
  biological_processes:
  - preferred_term: positive regulation of transcription by RNA polymerase II
    modifier: ABNORMAL
    term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly supports the recurrent translocation and
      ASPSCR1-TFE3 fusion as defining disease biology.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven
      by the ASPSCR1::TFE3 fusion.
    explanation: >-
      The mechanistic study abstract supports ASPSCR1::TFE3 as the oncogenic
      driver fusion.
  downstream:
  - target: Angiogenic Tumor Program
    description: Aberrant transcriptional activity promotes angiogenic tumor biology
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:37029109
      reference_title: "ASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        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.
      explanation: >-
        Genetic loss-of-function experiments directly connect the fusion to
        angiogenesis-dependent in-vivo tumor development.
  - target: Mitochondrial Biology Program
    description: ASPSCR1-TFE3 transcriptional programs include mitochondrial biology.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        The ASPSCR1::TFE3 fusion propels the growth of alveolar soft part
        sarcoma by activating transcriptional programs that regulate
        proliferation, angiogenesis, mitochondrial biogenesis, and
        differentiation
      explanation: >-
        The mechanistic study directly attributes the mitochondrial-biogenesis
        program to the fusion.
  - target: Cyclin D1-CDK4 Cell-Cycle Dependency
    description: ASPSCR1-TFE3 transcriptional programs drive cyclin D1/CDK4-dependent proliferation
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Among the effector programs driven by ASPSCR1::TFE3, cell proliferation
        was driven by high levels of cyclin D1 expression.
      explanation: >-
        The functional study directly links the fusion-driven program to cyclin
        D1-dependent proliferation.
- name: Angiogenic Tumor Program
  biological_scale: CELLULAR
  description: >-
    Alveolar soft part sarcoma is typically highly vascular, with expression of
    angiogenic programs that support tumor growth and provide the rationale for
    antiangiogenic systemic therapies.
  cell_types:
  - preferred_term: endothelial cell
    term:
      id: CL:0000115
      label: endothelial cell
  biological_processes:
  - preferred_term: angiogenesis
    modifier: INCREASED
    term:
      id: GO:0001525
      label: angiogenesis
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      identifying the essential role of ASPSCR1::TFE3 in tumor cell viability
      by regulating core transcriptional programs involved in cell
      proliferation, angiogenesis, and mitochondrial biology.
    explanation: >-
      The mechanistic study directly links ASPSCR1::TFE3 to angiogenesis and
      cell-proliferation transcriptional programs.
  - reference: PMID:37029109
    reference_title: "ASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      ASPSCR1::TFE3 thus orchestrates higher ordered angiogenesis via modulating
      the SE activity.
    explanation: >-
      Epigenomic perturbation and in-vivo experiments establish a direct
      fusion-driven angiogenic program.
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Large peritumoral feeding vessels were systematically found and identified
      on ultrasonography (7/7), MRI (10/10), and CT (3/3).
    explanation: >-
      The imaging cohort supports the highly vascular tumor phenotype in
      patients.
  downstream:
  - target: Metastatic Progression
    description: Prominent angiogenic activity supports hematogenous metastatic progression.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - vascular-network construction and tumor-cell intravasation
    evidence:
    - reference: PMID:37029109
      reference_title: "ASPSCR1::TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        ASPS is characterized by a highly integrated vascular network, and its
        high metastatic potential indicates the importance of ASPS's prominent
        angiogenic activity.
      explanation: >-
        The mechanistic study supports angiogenesis as an important contributor
        to the tumor's metastatic phenotype, while the edge remains indirect.
- name: Mitochondrial Biology Program
  biological_scale: CELLULAR
  description: >-
    ASPSCR1-TFE3 regulates mitochondrial biology and mitochondrial biogenesis as
    part of the core oncogenic transcriptional program.
  biological_processes:
  - preferred_term: mitochondrion organization
    modifier: ABNORMAL
    term:
      id: GO:0007005
      label: mitochondrion organization
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by
      regulating core transcriptional programs involved in cell proliferation,
      angiogenesis, and mitochondrial biology.
    explanation: >-
      The mechanistic study identifies mitochondrial biology as a core
      ASPSCR1::TFE3 transcriptional program.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The ASPSCR1::TFE3 fusion propels the growth of alveolar soft part sarcoma
      by activating transcriptional programs that regulate proliferation,
      angiogenesis, mitochondrial biogenesis, and differentiation and can be
      therapeutically targeted to improve treatment.
    explanation: >-
      The paper's significance statement supports mitochondrial biogenesis as an
      activated ASPS transcriptional program.
- name: Cyclin D1-CDK4 Cell-Cycle Dependency
  biological_scale: CELLULAR
  description: >-
    Recent preclinical work shows that ASPSCR1-TFE3-driven transcriptional
    programs create a cyclin D1/CDK4-dependent proliferation state that may be
    targetable with CDK4/6 inhibition, especially in combination with
    angiogenesis inhibition.
  biological_processes:
  - preferred_term: cell cycle G1/S phase transition
    modifier: INCREASED
    term:
      id: GO:0044843
      label: cell cycle G1/S phase transition
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      cell proliferation was driven by high levels of cyclin D1 expression.
    explanation: >-
      This directly supports cyclin D1 as a cell-cycle effector of ASPS
      proliferation.
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
      xenografts.
    explanation: >-
      The xenograft result supports combined CDK4/6 and angiogenesis inhibition
      as a preclinical therapeutic vulnerability.
  downstream:
  - target: Deep Soft Tissue Mass
    description: Proliferative tumor-cell outgrowth produces the characteristic slow-growing deep soft tissue mass.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - tumor-cell proliferation and mass effect
    evidence:
    - reference: PMID:38291475
      reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The clinical symptoms mainly included painless enlarged masses in deep
        soft tissues.
      explanation: >-
        The clinicopathologic cohort supports the deep soft tissue mass as the
        clinical manifestation of proliferative ASPS outgrowth.
- name: Metastatic Progression
  biological_scale: ORGANISM
  description: >-
    Alveolar soft part sarcoma often follows an indolent primary course but can
    metastasize to the lungs, brain, bone, and other sites, sometimes years
    after initial diagnosis.
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The national study confirmed a unique feature of ASPS with frequent
      metastasis to the lung and brain but an indolent clinical course.
    explanation: >-
      Population registry data support the combination of indolent course and
      frequent lung/brain metastasis.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Alveolar soft part sarcoma (ASPS) is a rare, indolent soft tissue
      sarcoma, with a high predilection for systemic dissemination.
    explanation: >-
      A real-world clinical cohort supports the systemic dissemination
      tendency.
  downstream:
  - target: Pulmonary Metastases
    description: Hematogenous metastatic progression commonly seeds the lungs.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40171452
      reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The most common site of primary was the extremities (73%), and the most
        common sites of metastasis included the lungs (82%) and bones (21%).
      explanation: >-
        The cohort identifies lung metastasis as the dominant metastatic
        manifestation of ASPS progression.
  - target: Brain Metastases
    description: Systemic dissemination can involve the central nervous system.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40171452
      reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Brain metastasis was seen in 7 patients at baseline (25.9%).
      explanation: >-
        The cohort supports brain metastasis as a direct clinical manifestation
        of systemic ASPS dissemination.
  - target: Bone Metastases
    description: Systemic dissemination can involve skeletal sites.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:40171452
      reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The most common site of primary was the extremities (73%), and the most
        common sites of metastasis included the lungs (82%) and bones (21%).
      explanation: >-
        The cohort identifies bone metastasis as a recurrent skeletal
        manifestation of ASPS progression.
histopathology:
- name: Pseudoalveolar Organoid Architecture
  finding_term:
    preferred_term: pseudoalveolar organoid architecture
  diagnostic: true
  description: >-
    Tumors have nests or organoid groups of polygonal cells separated by
    delicate sinusoidal vasculature, producing the classic pseudoalveolar
    pattern.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The tumour cells within the nodules were arranged as organoid or
      glandular vesicle-like structures with abundant blood sinuses between
      vesicles
    explanation: >-
      The pathology cohort directly describes the characteristic nested,
      pseudoalveolar architecture and sinusoidal vasculature.
- name: PAS-Positive Diastase-Resistant Cytoplasmic Crystals
  finding_term:
    preferred_term: PAS-positive diastase-resistant cytoplasmic crystals
  diagnostic: true
  description: >-
    Periodic acid-Schiff-positive, diastase-resistant rod- or bar-shaped
    cytoplasmic crystals are characteristic and help distinguish ASPS from
    morphologic mimics, although they are not present in every tumor.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The tumour cells in 20 patients were PAS positive and contained
      rod-shaped crystals in the cytoplasm
    explanation: >-
      PAS-positive rod-shaped crystals were observed in 20 of 26 tumors in the
      pathology cohort.
phenotypes:
- category: Musculoskeletal
  name: Deep Soft Tissue Mass
  diagnostic: true
  description: >-
    Patients commonly present with a slow-growing deep soft tissue mass,
    especially in the extremities.
  phenotype_term:
    preferred_term: Deep soft tissue mass
    term:
      id: HP:0031459
      label: Soft tissue neoplasm
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The clinical symptoms mainly included painless enlarged masses in deep
      soft tissues.
    explanation: >-
      The clinicopathologic cohort directly supports a painless deep soft
      tissue mass presentation.
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      all tumors were deeply seated.
    explanation: >-
      The imaging cohort supports the deep location and large mass-like
      presentation.
- category: Respiratory
  name: Pulmonary Metastases
  description: >-
    Hematogenous spread commonly involves the lung and may be present at
    diagnosis or emerge after a long interval.
  phenotype_term:
    preferred_term: Neoplasm of the lung
    term:
      id: HP:0100526
      label: Neoplasm of the lung
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      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%).
    explanation: >-
      The national registry cohort directly supports lung metastasis during the
      disease course after localized ASPS.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common site of primary was the extremities (73%), and the most
      common sites of metastasis included the lungs (82%) and bones (21%).
    explanation: >-
      A contemporary real-world cohort also identifies lung as the most common
      metastatic site.
- category: Neurologic
  name: Brain Metastases
  description: >-
    Brain metastases are a recognized complication in advanced disease.
  phenotype_term:
    preferred_term: Neoplasm of the central nervous system
    term:
      id: HP:0100006
      label: Neoplasm of the central nervous system
  evidence:
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Brain metastasis was seen in 7 patients at baseline (25.9%).
    explanation: >-
      The real-world cohort supports brain metastasis as a notable ASPS
      complication.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Patients with brain metastasis were seen to have markedly poor outcomes.
    explanation: >-
      The same cohort supports clinical severity of brain metastasis in ASPS.
- category: Musculoskeletal
  name: Bone Metastases
  description: >-
    Bone is a recurrent metastatic site in advanced alveolar soft part sarcoma.
  phenotype_term:
    preferred_term: Bone metastases
    term:
      id: HP:0010622
      label: Neoplasm of the skeletal system
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      bone, n = 12
    explanation: >-
      The national registry cohort reports bone metastases in 14% of metastatic
      ASPS patients.
  - reference: PMID:40171452
    reference_title: "Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in North India."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common site of primary was the extremities (73%), and the most
      common sites of metastasis included the lungs (82%) and bones (21%).
    explanation: >-
      A contemporary real-world cohort reports bones as a common metastatic site.
progression:
- phase: Indolent primary growth with persistent metastatic risk
  age_range: Adolescence through adulthood
  notes: >-
    ASPS often progresses slowly, but localized disease retains a substantial
    long-term risk of distant spread. In a national registry cohort, 45% of
    localized cases later developed distant metastases, predominantly in lung.
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      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%).
    explanation: >-
      The population registry directly quantifies later metastatic progression
      after localized presentation.
- phase: Prognostic separation by metastatic status
  notes: >-
    Five-year disease-specific survival is substantially better for localized
    than metastatic disease; the national registry identified metastasis at
    presentation as the only adverse prognostic factor for disease-specific
    survival.
  evidence:
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      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).
    explanation: >-
      The registry directly reports stage-stratified five-year disease-specific
      survival.
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Metastasis at presentation was the only adverse prognostic factor for DSS
    explanation: >-
      The registry identifies metastatic presentation as its only adverse
      disease-specific-survival factor without overextending that result to
      other cohorts.
imaging_findings:
- name: Hypervascular Deep Soft-Tissue Mass
  modality: MRI
  imaging_finding_term:
    preferred_term: hypervascular deep soft-tissue mass with flow voids and feeding vessels
  spatial_extent: FOCAL
  diagnostic: false
  description: >-
    MRI commonly shows a deeply seated mass with high T2 signal, numerous flow
    voids, high internal vascularization, and large peritumoral feeding vessels.
    The finding is characteristic but not disease-specific and can mimic a
    vascular lesion.
  evidence:
  - reference: PMID:37987424
    reference_title: "Imaging Features of Alveolar Soft Part Sarcoma: Single Institution Experience and Literature Review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      the hallmark of ASPS imaging at presentation are the following
      characteristics: deep location, a slight hyperintense MRI SI on T1-WI and
      a hyperintense SI on T2-WI, numerous MRI flow voids, high internal
      vascularization, and large peritumoral feeding vessels.
    explanation: >-
      The imaging cohort and literature review directly define the characteristic
      MRI appearance.
biochemical:
- name: TFE3 Nuclear Immunoreactivity
  notes: >-
    Nuclear TFE3 immunohistochemistry can support the diagnosis when integrated
    with morphology and molecular confirmation of the ASPSCR1-TFE3 fusion.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement
      was detected in 12 patients.
    explanation: >-
      The clinicopathologic cohort directly supports TFE3 protein positivity
      and rearrangement testing as diagnostic features.
genetic:
- name: ASPSCR1-TFE3 Fusion - ASPSCR1 Partner
  gene_term:
    preferred_term: ASPSCR1
    term:
      id: hgnc:13825
      label: ASPSCR1
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  notes: >-
    ASPSCR1 is one partner in the recurrent somatic ASPSCR1-TFE3 fusion that
    defines alveolar soft part sarcoma.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly names ASPSCR1 as one partner in the defining
      ASPS fusion.
- name: ASPSCR1-TFE3 Fusion - TFE3 Partner
  gene_term:
    preferred_term: TFE3
    term:
      id: hgnc:11752
      label: TFE3
  relationship_type: SOMATIC_DRIVER
  variant_origin: SOMATIC
  notes: >-
    TFE3 is the transcription-factor partner in the recurrent somatic
    ASPSCR1-TFE3 fusion.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The neoplasm is characterized by a specific chromosomal translocation,
      der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion.
    explanation: >-
      The review abstract directly names TFE3 as one partner in the defining
      ASPS fusion.
treatments:
- name: Complete Surgical Resection
  description: >-
    Complete resection with negative margins is the preferred local therapy
    when disease is localized and technically resectable.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: surgical excision
    term:
      id: NCIT:C15232
      label: Excision
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Complete surgical resection remains the standard treatment strategy,
      whereas radiotherapy is indicated for patients with inadequate surgical
      margins or unresectable tumours.
    explanation: >-
      The review abstract directly supports complete surgical resection as the
      standard local treatment strategy.
- name: Radiation Therapy
  description: >-
    Radiation therapy can be used when surgical margins are inadequate or when
    tumors are unresectable.
  therapeutic_modality: RADIOTHERAPY
  treatment_term:
    preferred_term: Radiation Therapy
    term:
      id: NCIT:C15313
      label: Radiation Therapy
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Complete surgical resection remains the standard treatment strategy,
      whereas radiotherapy is indicated for patients with inadequate surgical
      margins or unresectable tumours.
    explanation: >-
      The same review abstract supports radiation therapy for inadequate
      margins or unresectable disease.
- name: Antiangiogenic Targeted Therapy
  description: >-
    Antiangiogenic tyrosine kinase inhibitors, including pazopanib, sunitinib,
    and cediranib, have clinical activity in advanced ASPS and align with the
    tumor's angiogenic transcriptional program.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: pazopanib
      term:
        id: CHEBI:71219
        label: pazopanib
    - preferred_term: sunitinib
      term:
        id: CHEBI:38940
        label: sunitinib
    - preferred_term: cediranib
  target_mechanisms:
  - target: Angiogenic Tumor Program
    treatment_effect: INHIBITS
    description: Antiangiogenic kinase inhibitors target vascular signaling that supports tumor growth.
    evidence:
    - reference: PMID:31160249
      reference_title: "Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        our finding of significant clinical activity with cediranib in this
        disease is an important step towards the goal of long-term disease
        control for these young patients.
      explanation: >-
        The randomized placebo-controlled trial supports clinical inhibition of
        the angiogenesis-dependent tumor program by cediranib.
  evidence:
  - reference: PMID:37626447
    reference_title: "Advances in treatment of alveolar soft part sarcoma: an updated review."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Although alveolar soft part sarcoma is refractory to conventional
      doxorubicin-based chemotherapy, monotherapy or combination therapy using
      tyrosine kinase inhibitors and immune checkpoint inhibitors have provided
      antitumor activity and emerged as new treatment strategies.
    explanation: >-
      The review abstract supports tyrosine kinase inhibitors as an active
      systemic treatment class in ASPS.
  - reference: PMID:35971085
    reference_title: "Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Prolonged survival was seen in patients who received pazopanib treatment
      (p = 0.045), but not in those who received doxorubicin-based cytotoxic
      chemotherapy.
    explanation: >-
      Registry data support pazopanib-associated prolonged survival in
      metastatic ASPS.
  - reference: PMID:31160249
    reference_title: "Cediranib in patients with alveolar soft-part sarcoma (CASPS): a double-blind, placebo-controlled, randomised, phase 2 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Median percentage change in sum of target marker lesion diameters for the
      evaluable population was -8·3% (IQR -26·5 to 5·9) with cediranib versus
      13·4% (IQR 1·1 to 21·3) with placebo (one-sided p=0·0010).
    explanation: >-
      The randomized placebo-controlled phase 2 trial provides direct evidence
      of cediranib antitumor activity despite the intrinsically indolent course
      of ASPS.
- name: Atezolizumab
  description: >-
    Anti-PD-L1 immune checkpoint inhibitor pharmacotherapy is an important
    systemic option for advanced ASPS, with prospective evidence for
    atezolizumab.
  therapeutic_modality: MONOCLONAL_ANTIBODY
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: Atezolizumab
      term:
        id: NCIT:C106250
        label: Atezolizumab
  evidence:
  - reference: PMID:37672694
    reference_title: "Atezolizumab for Advanced Alveolar Soft Part Sarcoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      An objective response was observed in 19 of 52 patients (37%), with 1
      complete response and 18 partial responses.
    explanation: >-
      The prospective phase 2 study supports atezolizumab activity in advanced
      ASPS.
  - reference: PMID:37672694
    reference_title: "Atezolizumab for Advanced Alveolar Soft Part Sarcoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Atezolizumab was effective at inducing sustained responses in
      approximately one third of patients with advanced ASPS.
    explanation: >-
      The study conclusion supports immune checkpoint blockade as an effective
      systemic option in a subset of advanced ASPS patients.
- name: Axitinib Plus Pembrolizumab
  description: >-
    Combined VEGFR tyrosine-kinase inhibition and PD-1 checkpoint blockade has
    prospective phase 2 activity in advanced ASPS but remains an investigational
    combination requiring randomized evaluation.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: axitinib
      term:
        id: CHEBI:66910
        label: axitinib
    - preferred_term: pembrolizumab
      term:
        id: NCIT:C106432
        label: Pembrolizumab
  target_mechanisms:
  - target: Angiogenic Tumor Program
    treatment_effect: INHIBITS
    description: Axitinib inhibits VEGF-receptor signaling while pembrolizumab relieves PD-1-mediated immune suppression.
    evidence:
    - reference: PMID:31078463
      reference_title: "Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        VEGF promotes an immunosuppressive microenvironment and contributes to
        immune checkpoint inhibitor resistance in cancer.
      explanation: >-
        This supplies the combination's angiogenesis/immune rationale; the
        trial did not isolate the contribution of either drug.
  evidence:
  - reference: PMID:31078463
    reference_title: "Axitinib plus pembrolizumab in patients with advanced sarcomas including alveolar soft-part sarcoma: a single-centre, single-arm, phase 2 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      For patients with ASPS, 3-month progression-free survival was 72·7% (95%
      CI 37·1-90·3).
    explanation: >-
      The ASPS subgroup result directly supports prospective activity of the
      combination while its single-arm design limits comparative inference.
- name: Investigational Combined CDK4/6 and Angiogenesis Inhibition
  description: >-
    Preclinical ASPS models support combining CDK4/6 inhibition with
    antiangiogenic inhibition. This strategy halted xenograft growth, but no
    clinical efficacy or safety inference can yet be made.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: palbociclib
      term:
        id: CHEBI:85993
        label: palbociclib
    - preferred_term: sunitinib
      term:
        id: CHEBI:38940
        label: sunitinib
  target_mechanisms:
  - target: Cyclin D1-CDK4 Cell-Cycle Dependency
    treatment_effect: INHIBITS
    description: Palbociclib inhibits CDK4/6-dependent tumor-cell proliferation.
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Disruption of cyclin D1/CDK4 signaling led to a loss of ASPS
        proliferative capacity
      explanation: >-
        Functional disruption directly supports the CDK4/6 dependency targeted
        by palbociclib.
  - target: Angiogenic Tumor Program
    treatment_effect: INHIBITS
    description: Antiangiogenic kinase inhibition targets the complementary vascular dependency.
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: >-
        combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
        xenografts.
      explanation: >-
        The xenograft result directly supports joint inhibition of the
        cell-cycle and angiogenic programs.
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
      xenografts.
    explanation: >-
      This directly supports the class-level preclinical combination strategy;
      it does not establish benefit in patients.
diagnosis:
- name: TFE3 Immunohistochemistry
  description: >-
    Nuclear TFE3 immunoreactivity supports ASPS in the correct morphologic
    context, but it is not fully specific and molecular confirmation is more
    sensitive and specific.
  diagnosis_term:
    preferred_term: immunohistochemical test
    term:
      id: NCIT:C51944
      label: Immunohistochemical Test
  evidence:
  - reference: PMID:26516944
    reference_title: Alveolar Soft Part Sarcoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      This translocation is diagnostically useful because the tumor nuclei are
      positive for TFE3 by immunohistochemistry.
    explanation: >-
      The pathology review supports nuclear TFE3 immunoreactivity as a useful
      diagnostic marker.
- name: ASPSCR1-TFE3 Fusion Transcript Testing
  description: >-
    Molecular detection of the defining ASPSCR1-TFE3 fusion by RT-PCR, RNA
    sequencing, or complementary rearrangement testing confirms the diagnosis
    when morphology and TFE3 immunohistochemistry suggest ASPS.
  diagnosis_term:
    preferred_term: reverse transcriptase-polymerase chain reaction
    term:
      id: NCIT:C19770
      label: Molecular Analysis
  evidence:
  - reference: PMID:26516944
    reference_title: Alveolar Soft Part Sarcoma.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Real-time polymerase chain reaction to detect the ASPSCR1-TFE3 fusion
      transcript on paraffin-embedded tissue blocks has been shown to be more
      sensitive and specific than detection of TFE3 by immunohistochemical
      stain.
    explanation: >-
      This directly supports fusion-transcript testing and its diagnostic
      advantage over TFE3 immunohistochemistry alone.
differential_diagnoses:
- name: Paraganglioma
  description: >-
    Paraganglioma can share nested, highly vascular morphology with ASPS.
  distinguishing_features:
  - Neuroendocrine-marker expression, including NSE, CgA, and synaptophysin, favors paraganglioma over ASPS.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      positivity for neuroendocrine markers such as NSE, CgA and Syn but not
      MyoD1, Des or others
    explanation: >-
      The pathology review provides the neuroendocrine immunophenotypic
      distinction from ASPS.
- name: Alveolar Rhabdomyosarcoma
  description: >-
    Alveolar rhabdomyosarcoma can mimic pseudoalveolar architecture, especially
    in children and adolescents.
  distinguishing_features:
  - Nuclear MyoD1 and other myogenic-marker expression favor alveolar rhabdomyosarcoma over ASPS.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Immunohistochemical findings for alveolar rhabdomyosarcoma include the
      following: tumour cells expressing myogenic markers such as Des and
      MyoD1, with MyoD1 observable in the nucleus
    explanation: >-
      Nuclear myogenic-marker expression distinguishes alveolar
      rhabdomyosarcoma from ASPS.
- name: Metastatic Clear Cell Renal Cell Carcinoma
  description: >-
    Metastatic clear cell renal cell carcinoma, including TFE3-rearranged renal
    carcinoma, may resemble ASPS morphologically and immunohistochemically.
  distinguishing_features:
  - A renal primary and expression of epithelial, CD10, and RCC markers favor metastatic renal cell carcinoma.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      renal cell carcinomas with the ASPSCR1::TFE3 fusion also express CK and
      EMA epithelial markers and are positive for CD10 and RCC.
    explanation: >-
      The epithelial and renal-marker profile distinguishes renal carcinoma
      from ASPS.
- name: Perivascular Epithelioid Cell Tumor
  description: >-
    PEComa may have organoid perivascular growth and can itself harbor TFE3
    rearrangements.
  distinguishing_features:
  - A TFE3 rearrangement alone does not exclude PEComa; identification of a non-ASPS fusion partner favors PEComa.
  evidence:
  - reference: PMID:38291475
    reference_title: "Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Recent studies have revealed the presence of TFE3 gene rearrangements in
      23% of PEComas, which involve the formation of gene fusions such as
      SFPQ/PSF::TFE3 and DVL2::TFE3.
    explanation: >-
      The pathology review supplies a clean, complete sentence showing that
      TFE3 rearrangement occurs in PEComa and identifies alternative partners.
clinical_trials:
- name: NCT03141684
  phase: PHASE_II
  description: >-
    Phase 2 trial of atezolizumab alone or atezolizumab plus bevacizumab for
    advanced unresectable ASPS.
  evidence:
  - reference: clinicaltrials:NCT03141684
    reference_title: "A Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Alveolar Soft Part Sarcoma"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This phase II trial studies how well atezolizumab or atezolizumab plus
      bevacizumab works in treating patients with alveolar soft part sarcoma
      that has not been treated, has spread from where it started to other
      places in the body (advanced) and cannot be removed by surgery
      (unresectable).
    explanation: >-
      ClinicalTrials.gov directly supports the atezolizumab plus/minus
      bevacizumab trial in advanced unresectable ASPS.
- name: NCT02636725
  phase: PHASE_II
  description: >-
    Phase 2 trial of combined axitinib and pembrolizumab in advanced ASPS and
    other soft tissue sarcomas.
  evidence:
  - reference: clinicaltrials:NCT02636725
    reference_title: "A Phase II Trial of Concurrent Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma (ASPS) and Other Soft Tissue Sarcomas (STS)"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of this research study is to test if Axitinib together with
      Pembrolizumab can slow tumor growth and know the side effects of the
      combination treatment.
    explanation: >-
      ClinicalTrials.gov directly supports investigation of combined axitinib
      and pembrolizumab.
- name: NCT01391962
  phase: PHASE_II
  description: >-
    Randomized phase 2 trial of cediranib versus sunitinib monotherapy with
    crossover at progression in metastatic ASPS.
  evidence:
  - reference: clinicaltrials:NCT01391962
    reference_title: "A Phase II Trial In Which Patients With Metastatic Alveolar Soft Part Sarcoma Are Randomized to Either Sunitinib or Cediranib Monotherapy, With Cross-Over at Disease Progression"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Determine the objective response rate (ORR) of single-agent cediranib and
      single-agent sunitinib malate in patients with advanced ASPS.
    explanation: >-
      ClinicalTrials.gov directly supports this VEGFR TKI comparison trial in
      advanced ASPS.
- name: NCT01337401
  phase: PHASE_II
  description: >-
    International randomized double-blind placebo-controlled phase 2 CASPS
    trial of cediranib in metastatic ASPS, subsequently reported in the
    peer-reviewed randomized trial publication.
  evidence:
  - reference: clinicaltrials:NCT01337401
    reference_title: A Phase II Trial of Cediranib in the Treatment of Patients With Alveolar Soft Part Sarcoma (CASPS)
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The study is a two-arm, randomised, double-blind, international,
      multi-centre phase II trial of cediranib in Alveolar Soft Part Sarcoma
      (ASPS).
    explanation: >-
      ClinicalTrials.gov directly supports the CASPS design and disease scope.
animal_models:
- species: Mus musculus
  genotype: ASPS tumor xenograft and patient-derived xenograft models
  genes:
  - preferred_term: ASPSCR1
    term:
      id: hgnc:13825
      label: ASPSCR1
  - preferred_term: TFE3
    term:
      id: hgnc:11752
      label: TFE3
  description: >-
    Mouse xenograft models carrying ASPSCR1::TFE3-positive ASPS were used to
    test fusion-dependent tumor biology and combined CDK4/6 and angiogenesis
    inhibition. They model tumor growth and drug response but do not establish
    efficacy or safety in patients.
  associated_phenotypes:
  - Angiogenesis-dependent tumor development
  - Cyclin D1-CDK4-dependent proliferation
  - Tumor-growth arrest with combined CDK4/6 and angiogenesis inhibition
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      combined inhibition of CDK4/6 and angiogenesis halted tumor growth in
      xenografts.
    explanation: >-
      The xenograft experiment directly supports the model's combination-drug
      response while remaining preclinical.
experimental_models:
- name: ASPSCR1-TFE3-Positive ASPS Tumor Cell Lines
  description: >-
    Human ASPS tumor-cell lines and fusion perturbation systems model the
    transcriptional, chromatin, proliferative, angiogenic, and mitochondrial
    programs controlled by ASPSCR1::TFE3. Cell culture cannot reproduce the
    integrated human tumor microenvironment or establish clinical efficacy.
  experimental_model_type: CELL_LINE
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  cell_source: Human ASPS tumor-derived cell lines
  culture_system: Monolayer cell culture with genetic and pharmacologic perturbation
  conditions:
  - ASPSCR1::TFE3 expression or disruption
  - cyclin D1/CDK4 pathway disruption
  publication: PMID:38657118
  modeled_mechanisms:
  - target: ASPSCR1-TFE3 Fusion Oncogene
    description: Models fusion-dependent transcriptional and chromatin regulation.
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        ASPSCR1::TFE3 directly interacted with key epigenetic regulators at
        enhancers and promoters to support ASPS-associated transcription.
      explanation: >-
        The cell-based mechanistic study directly supports fusion-dependent
        transcriptional regulation.
  - target: Cyclin D1-CDK4 Cell-Cycle Dependency
    description: Models loss of proliferative capacity after cyclin D1/CDK4 disruption.
    evidence:
    - reference: PMID:38657118
      reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: >-
        Disruption of cyclin D1/CDK4 signaling led to a loss of ASPS
        proliferative capacity
      explanation: >-
        Functional perturbation directly supports the modeled cell-cycle
        dependency.
  evidence:
  - reference: PMID:38657118
    reference_title: "ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      we characterized the transcriptional and chromatin landscapes of ASPS
      tumors and preclinical models
    explanation: >-
      The publication directly documents use of preclinical models to map ASPS
      transcriptional and chromatin biology.
notes: >-
  Falcon deep research emphasized the ASPSCR1-TFE3 fusion, angiogenic tumor
  biology, high lung and brain metastatic burden, atezolizumab clinical
  activity, and emerging preclinical CDK4/6 vulnerability. Report citations
  were mapped to PMID-backed caches where possible before YAML evidence was
  added.
datasets:
- accession: geo:GSE235739
  title: ASPSCR1::TFE3 Drives Alveolar Soft Part Sarcoma by Inducing Targetable Transcriptional Programs
  description: This SuperSeries is composed of the SubSeries listed below. Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy driven by the ASPSCR1::TFE3 fusion. A better understanding of the mechanisms by which this oncogenic transcriptional regulator drives cancer growth is needed to help identify potential therapeutic targets. Here, we characterized the transcriptional and chromatin landscapes of ASPS tumors and preclinical models, identifying the essential role of ASPSCR1::TFE3 in tumor cell viability by regulating core transcriptional programs involved in cell proliferation, angiogenesis, and mitochondrial biology.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: MULTI_OMICS
  sample_count: 62
  publication: PMID:38657118
  notes: Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE186789
  title: ASPSCR1-TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma I
  description: Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis.
  data_type: MICROARRAY
  sample_count: 27
  publication: PMID:37029109
  notes: Identified by GEO DataSets index search for Alveolar Soft Part Sarcoma (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
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References & Deep Research

Deep Research

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Disease Characteristics Research Template
Edison Scientific Literature 28 citations 2026-05-09T10:32:00.013707

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Alveolar Soft Part Sarcoma
  • MONDO ID: (if available)
  • Category: Cancer

Research Objectives

Please provide a comprehensive research report on Alveolar Soft Part Sarcoma covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
  • Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Alveolar Soft Part Sarcoma (ASPS): Disease Characteristics Research Report (2026-05-09)

Executive summary

Alveolar soft part sarcoma (ASPS) is an ultra-rare, translocation-defined soft-tissue sarcoma driven by the ASPSCR1::TFE3 fusion that typically presents as a slow-growing, deeply located soft-tissue mass in adolescents and young adults, but with a high propensity for early or eventual metastasis—most commonly to lung, bone, and brain. Recent practice-changing progress includes durable responses to immune checkpoint blockade, notably atezolizumab, with an objective response rate (ORR) of 37% and median progression-free survival (PFS) of 20.8 months in a 2023 phase 2 study that underpinned regulatory approval. Concurrently, mechanistic 2024 work has clarified fusion-driven transcriptional programs and identified targetable dependencies (Cyclin D1/CDK4) that rationalize combination strategies with anti-angiogenic therapy.

Evidence summary table

The following table consolidates disease identity, clinicopathology, diagnostics, imaging, molecular biology, and the most recent outcome statistics extracted from the tool-retrieved evidence.

Domain Item Key details / quantitative values Evidence
Disease identity Definition Ultra-rare, translocation-defined soft-tissue sarcoma characterized by der(17)t(X;17)(p11.2;q25) creating the ASPSCR1::TFE3 fusion; typically indolent but highly metastatic and often vascular. Incidence reported as ~1 per 10 million population/year and 0.2–0.9% of soft-tissue sarcomas. (fujiwara2023advancesintreatment pages 1-2)
Disease identity Preferred name / synonym Alveolar soft part sarcoma (ASPS); literature also refers to alveolar soft-part sarcoma. Fusion historically described as ASPL-TFE3 / TFE3-ASPL in older literature. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Disease identity Identifiers available from retrieved evidence Retrieved evidence supports disease name and molecular definition, but MONDO, Orphanet, ICD-10/ICD-11, MeSH, and OMIM identifiers were not directly retrieved in the gathered evidence set; these should be added from ontology resources separately. (fujiwara2023advancesintreatment pages 1-2)
Clinicopathology Age distribution Peak age 15–35 years; SEER-based review reports median age 25 years, 72% <30 years. Recent cohorts: mean 27.1 ± 10.7 y (Spinnato 2023, n=12), median 27.5 y (Zhang 2024, n=26), median 28 y (Fernandes 2024, n=34). (fujiwara2023advancesintreatment pages 1-2, spinnato2023imagingfeaturesof pages 1-2, zhang2024alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Clinicopathology Sex distribution Often slight female predominance: review reports 58% female and approximate male:female ratio ~1:1.5; however real-world 2024 Indian cohort showed slight male predominance (19 M / 15 F). (fujiwara2023advancesintreatment pages 1-2, cong2025recentprogressin pages 1-2, fernandes2024realworldoutcomes pages 1-2)
Clinicopathology Primary sites Most common sites: extremities 61%, trunk 20%, head/neck 9%, internal organs 8% in review data. In Fernandes 2024, 73% arose in extremities. Pediatric series showed 50% head/neck and 50% trunk/limbs. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)
Clinicopathology Typical presentation Usually a slow-growing, painless deep soft-tissue mass; tumors are often highly vascular. Zhang 2024: painless enlarged masses in deep soft tissue; Spinnato 2023: all tumors were deeply seated with mean longest diameter 7.6 ± 2.9 cm. (zhang2024alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)
Clinicopathology Metastasis pattern Common metastatic sites are lung, bone, and brain. Japanese population study: metastatic cases had lung 99%, bone 14%, brain 11%; localized cases later developed distant metastases in 45%. Fernandes 2024: lung 82%, bone 21%, brain metastasis at baseline 25.9%. (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 1-2, fernandes2024realworldoutcomes pages 2-6)
Clinicopathology Metastasis at diagnosis High baseline dissemination: Spinnato 2023 8/12 (66.7%) metastatic at baseline; Fujiwara 2022 72% metastatic at presentation; Fernandes 2024 27/34 (79%) metastatic at presentation. Larger tumors were associated with metastasis in imaging cohorts. (spinnato2023imagingfeaturesof pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6)
Diagnostics Histopathology Classic morphology: organoid/nested epithelioid cells with pseudoalveolar architecture, abundant eosinophilic cytoplasm, sinusoidal vasculature; PAS-positive diastase-resistant crystalline material may be present. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 4-7)
Diagnostics PAS crystals / PAS positivity Review data describe PAS-positive glycogen and rod-shaped crystals as characteristic. In Zhang 2024, 20/26 tumors were PAS-positive. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 4-7)
Diagnostics TFE3 immunohistochemistry Nuclear TFE3 staining is a major diagnostic hallmark. Zhang 2024: 24/26 (92.3%) TFE3-positive. Review literature describes sensitivity often >95%, but specificity is imperfect and false positives can occur. (zhang2024alveolarsoftpart pages 2-4, zhang2024alveolarsoftpart pages 4-7, cong2025recentprogressin pages 4-5)
Diagnostics Fusion event Pathognomonic chromosomal abnormality: der(17)t(X;17)(p11.2;q25) producing ASPSCR1::TFE3 fusion. This is the key molecular defining event in ASPS. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)
Diagnostics Fusion testing methods Molecular confirmation can be performed by FISH, RT-PCR, and increasingly RNA sequencing/NGS. Zhang 2024: 12/12 tested showed TFE3 rearrangement by FISH in the tested subset. (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 3-4, cong2025recentprogressin pages 4-5)
Imaging Characteristic imaging hallmarks MRI: slight/mild T1 hyperintensity, T2 hyperintensity, frequent flow voids, peritumoral edema; US: well-defined hypoechoic heterogeneous lesion with abundant Doppler flow; large peritumoral feeding vessels seen on US/MRI/CT. (spinnato2023imagingfeaturesof pages 1-2, spinnato2023imagingfeaturesof pages 8-10, spinnato2023imagingfeaturesof pages 2-4)
Imaging Imaging risk marker In Spinnato 2023, tumor size >5 cm was associated with metastasis at diagnosis (p=0.01), with OR 45.0 (95% CI 1.49–1358.36, p=0.0285). Pediatric US study found moderate correlation between size and metastasis risk (r=0.64). (spinnato2023imagingfeaturesof pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)
Molecular pathogenesis Core biology ASPSCR1::TFE3 is essential for tumor cell viability and drives transcriptional programs in proliferation, angiogenesis, mitochondrial biology, and differentiation; it engages enhancer/promoter complexes and epigenetic regulators. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9)
Molecular pathogenesis Targetable downstream dependencies 2024 mechanistic work identified Cyclin D1/CDK4 dependence and showed palbociclib reduced proliferation; palbociclib + sunitinib was more effective than either alone in xenografts. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)
Treatment (recent) Atezolizumab phase 2 (NEJM 2023) Multicenter single-group phase 2; 52 evaluable patients. ORR 37% (19/52) = 1 CR + 18 PR; median time to response 3.6 mo; median duration of response 24.7 mo; median PFS 20.8 mo; no treatment-related grade 4/5 AEs. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 5-7, chen2023atezolizumabforadvanced pages 7-8)
Treatment (recent) Atezolizumab regulatory relevance / implementation Study formed the basis for FDA approval of atezolizumab for advanced ASPS in late 2022; ongoing trial platform continues as NCT03141684 (atezolizumab alone or with bevacizumab). (chen2023atezolizumabforadvanced pages 1-3, NCT03141684 chunk 2, NCT03141684 chunk 3)
Treatment (real-world) TKI outcomes in Fernandes 2024 In metastatic ASPS, 90% received first-line TKI. Median PFS 12 mo overall for first-line TKI monotherapy; sunitinib ORR 36%, disease-control rate 64%; median PFS numerically 15 vs 11 mo for sunitinib vs non-sunitinib TKIs. (fernandes2024realworldoutcomes pages 2-6, fernandes2024realworldoutcomes pages 6-8)
Treatment (real-world) ICI outcomes in Fernandes 2024 7 advanced-disease patients received ICIs (3 atezolizumab, 4 nivolumab). Atezolizumab produced prolonged disease control in some patients (progression-free at 20 and 15 months in cohort summary). Nivolumab included one ongoing complete metabolic response with duration ~52 months. (fernandes2024realworldoutcomes pages 1-2, fernandes2024realworldoutcomes pages 2-6, fernandes2024realworldoutcomes pages 6-8)
Prognosis Population survival (Fujiwara 2022) In 120 Japanese patients, 5-year disease-specific survival (DSS) 68% overall, 86% localized, 62% metastatic (p=0.019). Metastasis at presentation was the only adverse prognostic factor (HR 7.65, p=0.048). (fujiwara2022alveolarsoftpart pages 1-2)
Prognosis Additional cohort outcomes Fernandes 2024 metastatic cohort: median OS 36 mo, 3-year OS 52%; brain metastasis associated with poor survival (9.4 vs 56 mo, p=0.003). Zhang 2024: prognosis associated with sex (P=0.006), tumor size (P=0.031), and metastasis (P=0.043). (fernandes2024realworldoutcomes pages 2-6, zhang2024alveolarsoftpart pages 4-7, zhang2024alveolarsoftpart pages 2-4)
Trials / current implementation Active and landmark trial programs Key ASPS systemic-therapy trials include NCT03141684 (atezolizumab ± bevacizumab), NCT02636725 (axitinib + pembrolizumab), and NCT01391962 (randomized phase 2 cediranib vs sunitinib; actual enrollment 34). (NCT03141684 chunk 2, NCT02636725 chunk 2, NCT01391962 chunk 1)

Table: This table condenses the most actionable disease-level evidence for alveolar soft part sarcoma, including identity, clinicopathologic characteristics, diagnostic hallmarks, and the most important recent treatment and survival data. It is designed to support knowledge-base population with quantitative facts and direct evidence links.

1. Disease information

1.1 Definition and overview

ASPS is an ultra-rare soft-tissue sarcoma characterized by a specific chromosomal translocation der(17)t(X;17)(p11.2;q25) producing the ASPSCR1::TFE3 fusion, with an indolent primary tumor behavior but marked metastatic potential. A recent review describes ASPS as “a rare neoplasm of uncertain histogenesis… characterized by a specific chromosomal translocation… that results in ASPSCR1–TFE3 gene fusion,” and summarizes typical sites (extremities/trunk/head–neck) and metastatic predilection (lung/bone/brain). (fujiwara2023advancesintreatment pages 1-2)

1.2 Key identifiers (OMIM, Orphanet, ICD, MeSH, MONDO)

Within the tool-retrieved evidence set, formal ontology identifiers (OMIM, Orphanet/ORPHA, ICD-10/ICD-11, MeSH, MONDO) were not captured in full text and therefore cannot be asserted without external ontology lookup. The disease name and its defining fusion lesion were consistently supported in the retrieved primary literature and reviews. (fujiwara2023advancesintreatment pages 1-2)

1.3 Synonyms and alternative names

Common written variants include “alveolar soft part sarcoma” and “alveolar soft-part sarcoma.” The canonical fusion has also been described historically as “ASPL-TFE3” or “TFE3-ASPL” in older literature; recent papers use ASPSCR1::TFE3. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 1-2)

1.4 Evidence source types

This report integrates aggregated evidence from population-based registries and retrospective cohorts (human clinical), prospective interventional trials (human clinical), and mechanistic preclinical models (in vitro, xenograft/PDX). (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6, chen2023atezolizumabforadvanced pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16)

2. Etiology

2.1 Disease causal factors

Primary causal factor (genetic/driver lesion): The defining lesion is an unbalanced t(X;17)(p11.2;q25) producing ASPSCR1::TFE3, a chimeric transcription factor essential for tumor viability. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

Mechanistic nature: ASPSCR1::TFE3 functions as an oncogenic transcriptional regulator that occupies active chromatin and coordinates programs including proliferation and angiogenesis. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9)

2.2 Risk factors

No specific inherited predisposition, environmental exposure, or infectious agent risk factors were identified in the retrieved evidence. The most consistent “risk” correlates relate to clinical factors associated with metastatic presentation (e.g., tumor size, deep location, and age >25 years in a registry cohort) rather than causal exposures. (fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)

2.3 Protective factors / gene–environment interactions

No protective factors or gene–environment interactions were identified in the retrieved evidence set.

3. Phenotypes (clinical presentation)

3.1 Common phenotypes and suggested HPO terms

Deep soft-tissue mass; often painless, slow-growing - Evidence: “The clinical symptoms mainly included painless enlarged masses in deep soft tissues.” (Zhang 2024) (zhang2024alveolarsoftpart pages 1-2) - Suggested HPO: - Soft tissue neoplasm (HP:0002664) - Painless mass (HP:0031509) (term availability may vary)

High vascularity / prominent feeding vessels (imaging phenotype) - Evidence: ASPS lesions show abundant intratumoral/peritumoral vascularity with prominent feeding vessels on US/MRI/CT. (spinnato2023imagingfeaturesof pages 1-2, spinnato2023imagingfeaturesof pages 8-10) - Suggested HPO (proxy imaging/vascular): - Increased vascularity (phenotype representation may be recorded clinically rather than as a specific HPO term)

Metastatic disease manifestations - Lung metastasis (common): registry and cohort data show lung as the dominant metastatic site. (fujiwara2022alveolarsoftpart pages 1-2, fernandes2024realworldoutcomes pages 2-6) - Brain metastasis (notable in ASPS): baseline brain metastasis 25.9% in one real-world cohort with poor outcomes. (fernandes2024realworldoutcomes pages 2-6) - Suggested HPO: - Neoplasm metastasis (HP:0003002) - Pulmonary metastasis (HP:0031411) - Brain metastasis (HP:0007297)

3.2 Age of onset and progression

ASPS most commonly affects adolescents and young adults (peak ~15–35 years; SEER median age ~25; majority <30), and often follows an indolent course that can delay diagnosis, but with frequent metastasis at baseline or later. (fujiwara2023advancesintreatment pages 1-2, fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2)

3.3 Frequency and severity

Quantitative frequencies vary by cohort and ascertainment, but baseline metastasis rates are often high: - 72% metastatic at presentation in a Japanese registry (n=120). (fujiwara2022alveolarsoftpart pages 1-2) - 66.7% metastatic at baseline in an imaging cohort (n=12). (spinnato2023imagingfeaturesof pages 1-2) - 79% metastatic at presentation in a tertiary-care real-world cohort (n=34). (fernandes2024realworldoutcomes pages 2-6)

3.4 Quality of life impact

QoL instruments (EQ-5D/SF-36) were not reported in the retrieved evidence. QoL impact is inferred from tumor burden and metastatic complications (notably CNS involvement) but cannot be quantified here.

4. Genetic / molecular information

4.1 Causal genes and chromosomal abnormalities

  • ASPSCR1 and TFE3 are implicated via the defining fusion ASPSCR1::TFE3 produced by der(17)t(X;17)(p11.2;q25). (fujiwara2023advancesintreatment pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

4.2 Pathogenic variants and variant properties

ASPS is primarily driven by a somatic structural variant (fusion/translocation) rather than recurrent point mutations in the retrieved sources. - Variant class: structural rearrangement (fusion) - Origin: somatic (tumor) - Detection: FISH/RT-PCR/RNA-seq/NGS (methods discussed in recent pathology sources). (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 4-5)

Population allele frequencies (gnomAD/ExAC) are not applicable for a tumor-specific fusion.

4.3 Diagnostic biomarker performance (TFE3)

TFE3 nuclear immunohistochemistry (IHC) is a key marker, but practical specificity can vary; a recent clinicopathologic series reported TFE3 positivity in 24/26 (92.3%) cases. (zhang2024alveolarsoftpart pages 2-4)

4.4 Epigenetic / transcriptional regulation (recent mechanistic advance; 2024)

A 2024 Cancer Research study mapped ASPS transcriptional/chromatin landscapes and provides direct mechanistic statements in the abstract: - Quote: “ASPSCR1::TFE3 directly interacted with key epigenetic regulators at enhancers and promoters to support ASPS-associated transcription.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3) - Quote: “cell proliferation was driven by high levels of cyclin D1 expression.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3) - Therapeutic implication: “combined inhibition of CDK4/6 and angiogenesis halted tumor growth in xenografts.” (sicinska2024aspscr1tfe3drivesalveolar pages 1-3)

4.5 Disease–target associations (knowledge graph)

OpenTargets lists ASPS associations for TFE3 and angiogenesis-related targets (e.g., KDR/VEGFR2, FLT4/VEGFR3, PDGFRB), reflecting both biology and clinical development focus. (OpenTargets Search: Alveolar soft part sarcoma)

5. Environmental information

No specific environmental, lifestyle, or infectious causal contributors were identified in the retrieved evidence.

6. Mechanism / pathophysiology

6.1 Causal chain (current understanding)

1) Initiating lesion: somatic der(17)t(X;17) generates ASPSCR1::TFE3. (fujiwara2023advancesintreatment pages 1-2, sicinska2024aspscr1tfe3drivesalveolar pages 1-3) 2) Fusion-driven transcriptional amplification: ASPSCR1::TFE3 broadly binds active chromatin and sustains programs in cell cycle/proliferation, angiogenesis, and mitochondrial biology. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 8-9) 3) Tumor phenotype: highly vascular tumor microenvironment and slow-growing primary lesions, with high metastatic propensity (lung/bone/brain). (fujiwara2022alveolarsoftpart pages 1-2, spinnato2023imagingfeaturesof pages 1-2) 4) Clinical manifestations: painless deep mass; metastatic symptoms depend on organ involved; brain metastasis is an adverse clinical turning point in real-world cohorts. (fernandes2024realworldoutcomes pages 2-6)

6.2 Key molecular programs and targetable dependencies (2024)

Mechanistic evidence supports targetable tumor-intrinsic and tumor-extrinsic vulnerabilities: - Cyclin D1/CDK4 dependency: palbociclib decreased Ki-67 and halted tumor growth in ASPS PDX; CRISPR targeting supports dependency; CDK4/6 + VEGFR inhibition improved xenograft control. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14) - Angiogenesis program: ASPS super-enhancers and expression profiles include angiogenesis genes (e.g., VEGFA), consistent with clinical activity of anti-angiogenic TKIs. (sicinska2024aspscr1tfe3drivesalveolar pages 8-9, fernandes2024realworldoutcomes pages 2-6)

6.3 Suggested ontology terms

GO biological process (examples): - Angiogenesis (GO:0001525) - Regulation of transcription by RNA polymerase II (GO:0006357) - Cell cycle G1/S transition (GO:0044843) - Mitochondrial biogenesis (GO:0007005)

Cell types (CL, examples): - Mesenchymal cell (CL:0000134) - Endothelial cell (CL:0000115) (relevant to the vascular phenotype)

7. Anatomical structures affected

7.1 Primary anatomical sites

Most commonly deep soft tissues of extremities (often thigh), with additional sites including trunk and head/neck; pediatric cohorts show relatively more head/neck presentations. (fujiwara2023advancesintreatment pages 1-2, wang2024ultrasoundcharacteristicsof pages 1-2)

Suggested UBERON (examples): - Limb (UBERON:0002101) - Thigh (UBERON:0000978) - Head and neck region (UBERON:0000033)

7.2 Secondary organs (metastases)

  • Lung (dominant), bone, brain; liver also occurs in some series. (fujiwara2022alveolarsoftpart pages 1-2, zhang2024alveolarsoftpart pages 2-4, fernandes2024realworldoutcomes pages 2-6)

Suggested UBERON (examples): - Lung (UBERON:0002048) - Bone tissue (UBERON:0002481) - Brain (UBERON:0000955)

8. Temporal development

8.1 Onset

Typically adolescent/young adult onset (peak 15–35), but cases can occur across a wide age range. (fujiwara2023advancesintreatment pages 1-2, zhang2024alveolarsoftpart pages 2-4)

8.2 Progression and course

ASPS often shows slow primary growth but frequent metastasis at diagnosis and ongoing metastatic risk even after localized presentation. - Example: in a registry cohort of localized ASPS, 45% developed distant metastases later. (fujiwara2022alveolarsoftpart pages 1-2)

9. Inheritance and population

9.1 Epidemiology

  • Incidence estimate: ~1 per 10 million population per year (review-level estimate). (fujiwara2023advancesintreatment pages 1-2)
  • Proportion of soft-tissue sarcomas: ~0.2–0.9% (review-level). (fujiwara2023advancesintreatment pages 1-2)

Prevalence estimates were not provided in the retrieved evidence.

9.2 Inheritance

ASPS is not described as a Mendelian inherited disorder in the retrieved sources; it is primarily a sporadic cancer driven by a somatic fusion event.

9.3 Demographics

  • Sex: often female predominance reported in reviews, but cohort-to-cohort variation exists. (fujiwara2023advancesintreatment pages 1-2, fernandes2024realworldoutcomes pages 2-6)
  • Age: concentration in younger patients. (fujiwara2023advancesintreatment pages 1-2)

10. Diagnostics

10.1 Pathology and biomarkers

  • TFE3 IHC: 24/26 positive in a 2024 series; sensitivity high but specificity can vary. (zhang2024alveolarsoftpart pages 2-4, cong2025recentprogressin pages 4-5)
  • Molecular confirmation: FISH/RT-PCR/NGS for ASPSCR1::TFE3; Zhang 2024 detected TFE3 rearrangement in 12 tested patients. (zhang2024alveolarsoftpart pages 2-4)
  • PAS-positive crystals: 20/26 PAS-positive in Zhang 2024. (zhang2024alveolarsoftpart pages 4-7)

10.2 Imaging-based diagnosis (2023–2024 evidence)

ASPS is notable for hypervascular imaging patterns that can mimic vascular malformations. - MRI/US hallmarks (Spinnato 2023): Quote from abstract: “Large peritumoral feeding vessels were systematically found and identified on ultrasonography (7/7), MRI (10/10), and CT (3/3).” (spinnato2023imagingfeaturesof pages 1-2) - Pediatric ultrasound (Wang 2024) describes rich vascularity and misclassification as vascular lesions in some cases; tumors were 50% head/neck and 50% trunk/limbs, with 8/20 metastatic at diagnosis. (wang2024ultrasoundcharacteristicsof pages 1-2, wang2024ultrasoundcharacteristicsof pages 3-6)

10.3 Differential diagnosis

A structured differential diagnosis list was not fully extractable from the retrieved evidence set; however, the need for molecular confirmation (fusion testing) in TFE3-positive or equivocal cases is emphasized due to IHC variability. (cong2025recentprogressin pages 4-5)

11. Outcome / prognosis

11.1 Survival statistics (population-level)

A Japanese population-based study (2006–2017; n=120) reported: - “The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively.” (fujiwara2022alveolarsoftpart pages 1-2) - Metastasis at presentation was the only adverse prognostic factor (HR 7.65). (fujiwara2022alveolarsoftpart pages 1-2)

11.2 Real-world outcomes (2024)

A tertiary-center real-world cohort (2016–2023; n=34) reported: - Median PFS on first-line TKI monotherapy: 12 months; median OS in metastatic cohort: 36 months; 3-year OS: 52%. (fernandes2024realworldoutcomes pages 2-6) - Brain metastasis conferred markedly poor outcomes (OS 9.4 vs 56 months). (fernandes2024realworldoutcomes pages 2-6)

11.3 Prognostic factors

In a 2024 clinicopathologic series (n=26), prognosis was significantly correlated with sex, tumor size, and metastasis; multivariable Cox regression identified sex and metastasis as independent prognostic factors. (zhang2024alveolarsoftpart pages 4-7, zhang2024alveolarsoftpart pages 2-4)

12. Treatment

12.1 Standard local therapy

Complete surgical resection is described as the standard approach for localized disease, with radiotherapy considered for inadequate margins or unresectable tumors. (fujiwara2023advancesintreatment pages 1-2)

Suggested MAXO terms (examples): - Surgical excision (MAXO:0001025) - Radiotherapy (MAXO:0000647)

12.2 Systemic therapy: recent developments (prioritizing 2023–2024)

Atezolizumab (PD-L1 inhibitor) — pivotal 2023 evidence

A 2023 investigator-initiated multicenter single-group phase 2 study (NEJM; ClinicalTrials.gov NCT03141684) reported: - Quote: “An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses.” (chen2023atezolizumabforadvanced pages 1-3) - Quote: “the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months.” (chen2023atezolizumabforadvanced pages 1-3) - Safety: no treatment-related grade 4–5 AEs in the abstract; detailed excerpt indicates grade 3 potentially related AEs in 15% and no discontinuations due to AEs. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 7-8)

Real-world implementation: The same NEJM paper notes FDA approval of atezolizumab based on this study, and ongoing trial infrastructure includes atezolizumab alone or with bevacizumab (NCT03141684). (chen2023atezolizumabforadvanced pages 1-3, NCT03141684 chunk 2)

Visual evidence (trial efficacy figures): Waterfall plot and Kaplan–Meier PFS are provided from the NEJM report. (chen2023atezolizumabforadvanced media 37f80583, chen2023atezolizumabforadvanced media 591ab6cf)

Suggested MAXO terms: - Immune checkpoint inhibitor therapy (MAXO:0001481) - PD-L1 inhibitor therapy (MAXO term may vary by release)

Anti-angiogenic TKIs (VEGFR pathway) — real-world and trial infrastructure

A 2024 real-world cohort found most metastatic patients received TKIs first line, with median PFS 12 months and sunitinib ORR 36%. (fernandes2024realworldoutcomes pages 2-6)

A randomized phase 2 crossover trial comparing cediranib vs sunitinib (NCT01391962; enrollment 34) used ORR and 24-week PFS endpoints and required RECIST-defined progression prior to enrollment, reflecting the clinical need to benchmark TKI activity in ASPS. (NCT01391962 chunk 1)

Suggested MAXO terms: - Tyrosine kinase inhibitor therapy (MAXO:0000943) - Antiangiogenic therapy (MAXO:0000938)

Combination and next-step strategies (mechanism-informed)

A 2024 mechanistic study supports combined targeting of cell-intrinsic CDK4 dependence and cell-extrinsic angiogenesis: - Quote (preclinical): “the combination of palbociclib and sunitinib was significantly more effective than either therapy alone…” (sicinska2024aspscr1tfe3drivesalveolar pages 14-16) This motivates clinical exploration of CDK4/6 inhibitors with anti-angiogenic agents (clinical translation remains investigational in ASPS). (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)

Suggested MAXO: - CDK4/6 inhibitor therapy (MAXO term may vary)

12.3 Active/landmark clinical trials (selected)

  • NCT03141684 (NCI; started 2017): atezolizumab alone or atezolizumab + bevacizumab; ORR by RECIST v1.1 is the primary endpoint; includes biopsy and imaging procedures. (NCT03141684 chunk 2, NCT03141684 chunk 3)
  • NCT02636725 (PI Jonathan Trent; started 2016): axitinib + pembrolizumab phase 2 single-arm; requires measurable disease and RECIST-defined progression; requires serial core biopsies. (NCT02636725 chunk 2)
  • NCT01391962 (NCI; started 2011): randomized phase 2 cediranib vs sunitinib with crossover; primary endpoints include ORR and 24-week PFS. (NCT01391962 chunk 1)

13. Prevention

No primary prevention strategies are established for ASPS in the retrieved evidence. Secondary/tertiary prevention in practice involves early recognition of hypervascular deep soft-tissue masses, referral to sarcoma centers, and appropriate staging (including chest and, in selected contexts, brain imaging given non-trivial CNS involvement in some cohorts). (spinnato2023imagingfeaturesof pages 1-2, fernandes2024realworldoutcomes pages 2-6)

14. Other species / natural disease

No naturally occurring ASPS analogs in non-human species were identified in the retrieved evidence.

15. Model organisms / preclinical models

Mechanistic work uses ASPS cell lines and xenograft/PDX models. - A 2024 Cancer Research study reports palbociclib effects in ASPS PDX and combination efficacy with sunitinib in xenografts, supporting translational modeling for therapy development. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16, sicinska2024aspscr1tfe3drivesalveolar pages 13-14)

Recent developments (2023–2024) — key takeaways for a knowledge base

1) Checkpoint blockade is now a central systemic option in advanced ASPS: atezolizumab achieved ORR 37% with durable responses and median PFS 20.8 months, with favorable high-grade toxicity profile (no treatment-related grade 4–5 AEs), and served as the basis for regulatory approval. (chen2023atezolizumabforadvanced pages 1-3, chen2023atezolizumabforadvanced pages 7-8) 2) Real-world data confirm continued importance of anti-angiogenic TKIs and highlight CNS metastasis as a major adverse factor, with median OS 36 months in a heavily metastatic cohort and OS ~9.4 months in those with brain metastases. (fernandes2024realworldoutcomes pages 2-6) 3) Mechanistic 2024 data identify a targetable cell-cycle dependency (Cyclin D1/CDK4) and support combination strategies with angiogenesis inhibition, providing a rational next wave of trial design beyond single-agent VEGFR-TKIs and ICIs. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3, sicinska2024aspscr1tfe3drivesalveolar pages 14-16)

Limitations of the retrieved evidence for this template

  • Formal disease identifiers (MONDO/Orphanet/OMIM/ICD/MeSH) were not available in the retrieved full-text snippets; they should be added from dedicated ontology resources.
  • QoL metrics, prevalence estimates, and comprehensive differential diagnosis lists were not captured in the current evidence set.
  • Some citations above are based on tool-provided excerpts; if a downstream curation workflow requires PMIDs for every item, the DOI-anchored references provided here should be mapped to PMIDs via PubMed.

References

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  4. (zhang2024alveolarsoftpart pages 1-2): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  5. (cong2025recentprogressin pages 1-2): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  6. (wang2024ultrasoundcharacteristicsof pages 1-2): Siwei Wang, Yu Wang, Jiatong Xu, Qinghua Ren, Yanxiu Hu, Liqun Jia, and Xiaoman Wang. Ultrasound characteristics of alveolar soft part sarcoma in pediatric patients: a retrospective analysis. BMC Cancer, Dec 2024. URL: https://doi.org/10.1186/s12885-024-13262-x, doi:10.1186/s12885-024-13262-x. This article has 2 citations and is from a peer-reviewed journal.

  7. (fujiwara2022alveolarsoftpart pages 1-2): Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki, and Akira Kawai. Alveolar soft part sarcoma: progress toward improvement in survival? a population-based study. BMC Cancer, Aug 2022. URL: https://doi.org/10.1186/s12885-022-09968-5, doi:10.1186/s12885-022-09968-5. This article has 33 citations and is from a peer-reviewed journal.

  8. (fernandes2024realworldoutcomes pages 2-6): Sanal Fernandes, Sameer Rastogi, Kanu Priya Bhatia, Sindhura Chitikela, Shamim A Shamim, Shivanand Gammanagatti, and Adarsh Barwad. Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in north india. ecancermedicalscience, Dec 2024. URL: https://doi.org/10.3332/ecancer.2024.1813, doi:10.3332/ecancer.2024.1813. This article has 1 citations and is from a peer-reviewed journal.

  9. (zhang2024alveolarsoftpart pages 4-7): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  10. (zhang2024alveolarsoftpart pages 2-4): Yi Zhang, Yuchen Huang, Yanzi Qin, Ningning Yang, Panpan Yang, Nan Li, and Zhenzhong Feng. Alveolar soft part sarcoma: a clinicopathological and immunohistochemical analysis of 26 cases emphasizing risk factors and prognosis. Diagnostic Pathology, Jan 2024. URL: https://doi.org/10.1186/s13000-024-01450-z, doi:10.1186/s13000-024-01450-z. This article has 10 citations and is from a peer-reviewed journal.

  11. (cong2025recentprogressin pages 4-5): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  12. (sicinska2024aspscr1tfe3drivesalveolar pages 1-3): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  13. (cong2025recentprogressin pages 3-4): Nan Cong, Qi Shi, Qingyu Xu, and Lin Zhang. Recent progress in the clinicopathological characteristics of alveolar soft part sarcoma. Frontiers in Medicine, Dec 2025. URL: https://doi.org/10.3389/fmed.2025.1702870, doi:10.3389/fmed.2025.1702870. This article has 0 citations.

  14. (spinnato2023imagingfeaturesof pages 8-10): Paolo Spinnato, Nicolas Papalexis, Marco Colangeli, Marco Miceli, Amandine Crombé, Anna Parmeggiani, Emanuela Palmerini, Alberto Righi, and Giuseppe Bianchi. Imaging features of alveolar soft part sarcoma: single institution experience and literature review. Clinics and Practice, 13:1369-1382, Nov 2023. URL: https://doi.org/10.3390/clinpract13060123, doi:10.3390/clinpract13060123. This article has 16 citations.

  15. (spinnato2023imagingfeaturesof pages 2-4): Paolo Spinnato, Nicolas Papalexis, Marco Colangeli, Marco Miceli, Amandine Crombé, Anna Parmeggiani, Emanuela Palmerini, Alberto Righi, and Giuseppe Bianchi. Imaging features of alveolar soft part sarcoma: single institution experience and literature review. Clinics and Practice, 13:1369-1382, Nov 2023. URL: https://doi.org/10.3390/clinpract13060123, doi:10.3390/clinpract13060123. This article has 16 citations.

  16. (sicinska2024aspscr1tfe3drivesalveolar pages 14-16): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  17. (sicinska2024aspscr1tfe3drivesalveolar pages 8-9): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  18. (sicinska2024aspscr1tfe3drivesalveolar pages 13-14): Ewa Sicinska, Vijaya S.R. Kola, Joseph A. Kerfoot, Madeleine L. Taddei, Alyaa Al-Ibraheemi, Yi-Hsuan Hsieh, Alanna J. Church, Esther Landesman-Bollag, Yosef Landesman, and Matthew L. Hemming. Aspscr1::tfe3 drives alveolar soft part sarcoma by inducing targetable transcriptional programs. Cancer Research, 84:2247-2264, Apr 2024. URL: https://doi.org/10.1158/0008-5472.can-23-2115, doi:10.1158/0008-5472.can-23-2115. This article has 11 citations and is from a highest quality peer-reviewed journal.

  19. (chen2023atezolizumabforadvanced pages 1-3): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  20. (chen2023atezolizumabforadvanced pages 5-7): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  21. (chen2023atezolizumabforadvanced pages 7-8): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  22. (NCT03141684 chunk 2): Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03141684

  23. (NCT03141684 chunk 3): Testing Atezolizumab Alone or Atezolizumab Plus Bevacizumab in People With Advanced Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2017. ClinicalTrials.gov Identifier: NCT03141684

  24. (fernandes2024realworldoutcomes pages 6-8): Sanal Fernandes, Sameer Rastogi, Kanu Priya Bhatia, Sindhura Chitikela, Shamim A Shamim, Shivanand Gammanagatti, and Adarsh Barwad. Real world outcomes in alveolar soft part sarcomas: experience with an ultra-rare sarcoma from a tertiary care centre in north india. ecancermedicalscience, Dec 2024. URL: https://doi.org/10.3332/ecancer.2024.1813, doi:10.3332/ecancer.2024.1813. This article has 1 citations and is from a peer-reviewed journal.

  25. (NCT02636725 chunk 2): Jonathan Trent, MD, PhD. Axitinib and Pembrolizumab in Subjects With Advanced Alveolar Soft Part Sarcoma and Other Soft Tissue Sarcomas. Jonathan Trent, MD, PhD. 2016. ClinicalTrials.gov Identifier: NCT02636725

  26. (NCT01391962 chunk 1): Alice Chen, M.D.. Sunitinib or Cediranib for Alveolar Soft Part Sarcoma. National Cancer Institute (NCI). 2011. ClinicalTrials.gov Identifier: NCT01391962

  27. (OpenTargets Search: Alveolar soft part sarcoma): Open Targets Query (Alveolar soft part sarcoma, 42 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

  28. (wang2024ultrasoundcharacteristicsof pages 3-6): Siwei Wang, Yu Wang, Jiatong Xu, Qinghua Ren, Yanxiu Hu, Liqun Jia, and Xiaoman Wang. Ultrasound characteristics of alveolar soft part sarcoma in pediatric patients: a retrospective analysis. BMC Cancer, Dec 2024. URL: https://doi.org/10.1186/s12885-024-13262-x, doi:10.1186/s12885-024-13262-x. This article has 2 citations and is from a peer-reviewed journal.

  29. (chen2023atezolizumabforadvanced media 37f80583): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.

  30. (chen2023atezolizumabforadvanced media 591ab6cf): Alice P. Chen, Elad Sharon, Geraldine O’Sullivan-Coyne, Nancy Moore, Jared C. Foster, James S. Hu, Brian A. Van Tine, Anthony P. Conley, William L. Read, Richard F. Riedel, Melissa A. Burgess, John Glod, Elizabeth J. Davis, Priscilla Merriam, Abdul R. Naqash, Kristin K. Fino, Brandon L. Miller, Deborah F. Wilsker, Asma Begum, Katherine V. Ferry-Galow, Hari A. Deshpande, Gary K. Schwartz, Brian H. Ladle, Scott H. Okuno, Jill C. Beck, James L. Chen, Naoko Takebe, Laura K. Fogli, Christina L. Rosenberger, Ralph E. Parchment, and James H. Doroshow. Atezolizumab for advanced alveolar soft part sarcoma. The New England journal of medicine, 389 10:911-921, Sep 2023. URL: https://doi.org/10.1056/nejmoa2303383, doi:10.1056/nejmoa2303383. This article has 167 citations and is from a highest quality peer-reviewed journal.