ASPS (Alveolar Soft Part Sarcoma) IHC Marker
The TFE3 antibody is the definitive IHC marker for diagnosing Alveolar Soft Part Sarcoma (ASPS), showing strong and diffuse nuclear positivity in this rare tumor. 1
Diagnostic Utility of TFE3 in ASPS
TFE3 immunostaining is the most specific and reliable marker for ASPS diagnosis, particularly when routine immunohistochemical markers fail to provide a characteristic immunoprofile 1
ASPS characteristically demonstrates strong and diffuse nuclear positivity for TFE3 antibody, which correlates with the underlying molecular abnormality 1
The molecular basis for TFE3 positivity is the ASPL-TFE3 gene fusion resulting from der(17)t(X;17)(p11.2;q25) translocation, which is pathognomonic for ASPS 1
Clinical Context and Diagnostic Challenges
ASPS is an uncommon neoplasm of uncertain histogenesis that typically presents as a painless, slow-growing mass with early metastatic potential 1
The tumor can present diagnostic challenges because it may give rise to a wide differential diagnosis, including both primary and metastatic neoplasms, especially when presenting in unusual locations such as cutaneous metastases 1
Routine immunohistochemical panels often fail to show characteristic patterns in ASPS, making TFE3 testing essential when this diagnosis is suspected 1
Diagnostic Algorithm for Suspected ASPS
When encountering a tumor with alveolar architecture and uncertain differentiation:
First, apply routine IHC markers to exclude more common diagnoses (epithelial markers like cytokeratins, mesenchymal markers like vimentin) 2
If routine markers are non-contributory and morphology suggests ASPS, proceed directly to TFE3 immunostaining 1
Confirm TFE3-positive cases with molecular testing for ASPL-TFE3 fusion to definitively establish the diagnosis 1
Important Caveats
TFE3 is not entirely specific to ASPS; it can also be positive in other translocation-associated renal cell carcinomas and some perivascular epithelioid cell tumors (PEComas) 3
The clinical and radiological context must be integrated with IHC findings, as ASPS typically presents with characteristic imaging features including high vascularity 1
Always correlate TFE3 positivity with morphologic features (alveolar/organoid architecture, abundant cytoplasm, periodic acid-Schiff-positive diastase-resistant crystals) to avoid misdiagnosis 1