CPM, 12q15, for Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Supporting a diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor
Additional Tests Lists test(s) that are always performed, at an additional charge, with the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|60254||AP Special Studies Review||No||Yes|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
This test is performed in conjunction with 60254 / Anatomic Pathology Special Studies Review. Additional testing may be performed after review by pathologist. Upon approval from the requesting clinician, 60254 / Anatomic Pathology Special Studies Review could be changed to 70012 / Pathology Consultation, if determined to be more appropriate.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Fluorescence In Situ Hybridization (FISH) with DNA Probes
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
CPM, 12q15, FISH
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.
A pathology/diagnostic report and a brief history are required.
Preferred: Formalin-fixed, paraffin-embedded (FFPE) tissue
Acceptable: Unstained glass, "positively charged" slides with FFPE tissue; slides may be stained and/or scraped
1. Process all specimens into FFPE blocks prior to submission.
2. If submitting slides, a minimum of ten, 4- to 5-micron thick, unstained slides are required if also requesting a Surgical Pathology Consultation; a minimum of three, 4- to 5-micron thick, unstained slides are required if not requesting a Surgical Pathology Consultation.
1. A quality specimen is essential for evaluation. Submit only tissue containing tumor cells; minimal tissue is required for evaluation.
2. Special stains performed outside Mayo Medical Laboratories and included with the case may be repeated and charged at the reviewing pathologist's discretion. Testing requested by referring physician may not be performed if deemed unnecessary by Mayo Clinic pathologist.
Forms: If not ordering electronically, submit a Pathology/Cytology Request Form (Supply T246) with the specimen.
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
The histological discrimination of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT) from lipoma can be diagnostically challenging. However, standard cytogenetic identification of ring and giant rod chromosomes strongly support the diagnosis of WDL/ALT. These abnormal chromosomes are mainly composed of amplified sequences derived from chromosome bands 12q13-15, and contain several amplified genes including MDM2, CPM, CDK4, and TSPAN31. MDM2 is amplified in >99% of WDL, and up to 30% of other types of sarcomas. The CPM gene encodes carboxypeptidase M, a membrane-bound arginine/lysine carboxypeptidase. CPM is located only 11 kb upstream from MDM2, and is consistently coamplified with MDM2 in WDL/ALT.(1) Similar to MDM2, this gene has been observed to be amplified in virtually all cases of WDL/ALT, but not in lipomas.
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.
0-9% amplified cells
An interpretive report will be provided.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for the CPM FISH probe (positive result).
A positive result is consistent with amplification of the CPM gene locus on 12q13-15 and supports the diagnosis of well-differentiated liposarcoma/atypical lipomatous tumor (WDL/ALT).
A negative result is consistent with absence of amplification of the CPM gene locus on 12q13-15. However, negative results do not exclude the diagnosis of WDL/ALT. Amplification varies in individual tumors and among different cells in the same tumor.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Reliable results are dependent on adequate specimen collection and processing. This test has been validated on formalin-fixed, paraffin-embedded tissue; other types of fixatives are discouraged. Improper treatment of tissues, such as decalcification, may cause FISH failure.
Clinical diagnosis and/or therapy should not be based solely on this assay. The results should be considered in conjunction with clinical information and/or additional diagnostic tests.
Initial Mayo investigations on more than 200 lipomatous tumors demonstrated that CPM is coamplified with MDM2 in 100% of cases. A posterior blinded validation study was performed on 61 formalin-fixed, paraffin-embedded tissues including 19 liposarcoma tumors, 20 lipoma tumors, and 22 other tumors. Each specimen had been previously characterized by 2 soft tissue pathologists. Two technologists scored 100 interphase nuclei for each specimen (200 total cells/case). Results showed that 19 of the 19 well-differentiated liposarcoma/atypical lipomatous tumors (WDL/ALT) had amplification of CPM. Each of the 42 nonlipomatous and lipoma tumors yielded normal results (ie, negative for both rearrangement and amplification).
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Erickson-Johnson MR, Seys AR, Roth CW, et al: Carboxypeptidase M: a biomarker for the discrimination of lipoma from liposarcoma. Mod Pathol 2009 Dec;22(12):1541-1547
2. Jacob E, Erickson-Johnson MR, Wang X, et al: Assessment of MDM2 amplification using fluorescence in situ hybridization on paraffin-embedded tissue discriminates atypical lipomatous tumors from lipomas. Mod Pathol 2006;19:13A
Method Description Describes how the test is performed and provides a method-specific reference
Formalin-fixed, paraffin-embedded tissues are cut at 4 microns and mounted on positively-charged glass slides. Five slides are prepared, with 1 to 2 slides stained with hematoxylin and eosin (H and E); the other 3 are left as unstained slides. The selection of tissue and the identification of target areas on an 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. Abnormalities involving the CPM locus at 12q13-15 are detected using a FISH enumeration probe, CPM (Mayo Clinic developed), along with a reference probe, CEP 12 (Abbott Molecular). The probe design consists of DNA derived from bacterial artificial chromosomes (BACs) spanning the CPM locus region and labeled with Spectrum Orange (R) and CEP 12 (D12Z3), labeled in Spectrum Green (G). The probe set is applied to the appropriate target areas, denatured, and hybridized overnight. Two independent scorers analyze 100 interphase nuclei each (200 total). Normal interphase nuclei show 2R2G signals. Normal patterns also include 1R1G, 1R2G, and 2R1G. Abnormal nuclei will have 3 or more additional G with amplification of the R, meaning the R signals will be too many to count and indicating that CPM is amplified. If the cells have multiple copies of RG, but the ratio is 1:1, this is considered abnormal, but not positive. In cases of low level amplification, green and red signals of 100 cells are recorded. If the ratio of G:R is 1:>3 the sample is called positive, if the ratio G:R is 1:2-3 then it is called low level amplification, if the ratio of G:R is 1:<2 the sample is called negative. Rarely, cases cannot be classified as neither positive nor negative; for these cases, the sample is called indeterminate. If the results of the 2 observers are comparable, the result is reported as positive or negative for amplification of the CPM locus 12q13-15 according to the 2005 ISCN nomenclature. The results are interpreted and reported by a working group pathologist.(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.
Monday through Friday; 8 a.m.-4:30 p.m.
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
1 week/7 days
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.
CPM, 12q15, for Well-Differentiated Liposarcoma/Atypical Lipomatous Tumor, FISH
88368 x 2-Morphometric analysis, in situ hybridization (quantitative or semi-quantitative) each probe; manual
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|
|89366||CPM, 12q15, FISH||In Process|