Alveolar Soft Part Sarcoma (ASPS)/Renal Cell Carcinoma (RCC), Xp11.23 (TFE3), FISH, Tissue
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Aids in the diagnosis of alveolar soft-part sarcoma or renal cell carcinoma variant when used in conjunction with an anatomic pathology consultation
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
TFE3, Xp11.23, FISH, Ts
Papillary renal cell carcinoma
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Provide a pathology report with each tissue specimen. The laboratory will not reject a specimen that arrives without this information but will hold the specimen until a pathology report is received.
Preferred: Formalin-fixed, paraffin-embedded tissue block
Acceptable: 5 unstained, 5-micron thick sections
Collection Instructions: Include 1 hematoxylin and eosin-stained slide.
Forms: If not ordering electronically, submit a Cytogenetics Hematologic Disorders Request Form (Supply T607) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Paraffin-embedded whole tissue or four 5-micron thick sections plus 1 hematoxylin and eosin slide
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Alveolar soft-part sarcoma (ASPS) is a rare malignant tumor typically occurring in patients in their 20s to 30s within the muscle and deep tissues of the extremities. ASPS is slow growing and refractory to chemotherapy with a propensity to metastasize. Prolonged survival is possible even with metastasis, although the long-term disease-related mortality rate is high. ASPS is characterized by a translocation that results in fusion of TFE3 on chromosome Xp11.2 with ASPSCR1 (also called ASPL or RCC17) on chromosome 17q25.3.(1,2) Both balanced and unbalanced forms (loss of the derivative X chromosome) of the translocation have been observed.(2,3)
Another tumor, a rare subset of papillary renal cell carcinoma (RCC) with a distinctive pathologic morphology, has rearrangements of TFE3 with ASPSCR1 or other fusion partner genes.(1,4,5) This tumor predominantly affects children and young adults, presents at an advanced stage but with an indolent clinical course, and is a distinct entity in the World Health Organization classification.(6) Typically a balanced form of the translocation is present in the RCC variant. An assay to detect rearrangement of TFE3 is useful to resolve diagnostic uncertainty in these tumor types, as immunohistochemistry for TFE3 is not reliable.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
A neoplastic clone is detected when the percent of nuclei with the abnormality exceeds the established normal cutoff for the TFE3 probe set. A positive result of TFE3 rearrangement is consistent with a diagnosis of alveolar soft-part sarcoma (ASPS) or renal cell carcinoma (RCC) variant. A negative result suggests that TFE3 is not rearranged, but does not exclude the diagnosis of ASPS or RCC variant.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not approved by the FDA and it is best used as an adjunct to existing clinical and pathologic information.
FISH analysis was performed on 25 normal samples from each gender (50 total), 12 tumor samples classified by a pathologist (10 alveolar soft-part sarcoma: ASPS; 2 renal cell carcinoma: RCC variant), and 9 tumors in the differential diagnosis in a blinded manner using standard sample processing techniques and FISH methodology.
No rearrangements of TFE3 were identified in 50 normal patient specimens or 9 tumor mimics. Of the 10 ASPS cases, 4 did not have a rearrangement, 2 had a balanced TFE3 separation, and 4 had an atypical TFE3 separation (presence of 2 normal X chromosomes and the derivative 17, but loss of the derivative X). This atypical rearrangement was confirmed using a TFE3/ASPSCR1 probe set. Of the 2 diagnostic RCC cases, 1 was normal and 1 had an atypical TFE3 separation, but reflex testing with the TFE3/ASPSCR1 probe was not possible due to insufficient sample.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Zhong M, De Angelo P, Osborne L, et al: Dual-color break-apart FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of Xp11 translocation renal cell carcinoma and alveolar soft part sarcoma. Am J Surg Pathol 2010;34(6):757-766
2. Ladanyi M, Lui MY, Antonescu CR, et al: The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25. Oncogene 2001;20:48-57
3. Williams A, Bartle G, Vaiyapuri SP, et al: Detection of ASPL/TFE3 fusion transcripts and the TFE3 antigen in formalin-fixed, paraffin-embedded tissue in a series of 18 cases of alveolar soft part sarcoma: Useful diagnostic tools in cases with unusual histologic features. Virchows Arch 2011;458:291-300
4. Ross H, Argani P: Xp11 translocation renal cell carcinoma. Pathology 2010;42(4):369-373
5. Armah HB, Parwani AV: Xp11.2 translocation renal cell carcinoma. Arch Pathol Lab Med 2010;134:124-129
6. WHO Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs In IARC WHO Classification of Tumours. Edited by JN Eble, et al. Lyon: IARC Press, 2004, pp 37-38
Method Description Describes how the test is performed and provides a method-specific reference
The test uses a laboratory-developed TFE3 tricolor break-apart (BAP) FISH probe strategy (red 5' TFE3, green 3' TFE3, and aqua X centromere). Reflex testing using a TFE3/ASPSCR1 probe set (green 3' TFE3, red ASPSCR1, and aqua X centromere) is performed when atypical TFE3 separation is detected. Formalin-fixed, paraffin-embedded tissues are cut at 5 microns and mounted on positively-charged glass slides. Three unstained slides and 1 slide stained with hematoxylin and eosin (H and E) are obtained. The selection of tissue and the identification of target areas on the H and E stained slide are performed by a pathologist. Using the H and E slide as a reference, target areas are etched with a diamond-tipped etcher on the back of the unstained slide to be assayed. The probe set is hybridized and 2 technologists analyze 50 interphase nuclei each (100 total) with the results expressed as percent of abnormal nuclei.(Unpublished Mayo method)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m. CST.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
Alveolar Soft Part Sarcoma (ASPS)/Renal Cell Carcinoma (RCC), Xp11.23 (TFE3), FISH, Tissue
88271 x 3-Molecular cytogenetics (eg, FISH), each probe
88275-Interphase in situ hybridization, 100-300 cells
88291-Interpretation and report
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|CG600||Reason For Referral||42349-1|