Cutaneous Anaplastic Large Cell Lymphoma, 6p25.3 (IRF4) Rearrangement, FISH, Tissue
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Supporting the diagnosis of cutaneous anaplastic large cell lymphoma when coordinated with a consultation by anatomic pathology
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
This test does not include a pathology consultation. If a pathology consultation is requested, 70012 Pathology Consultation should be ordered and the appropriate FISH test will be ordered and performed at an additional charge.
Fluorescence In Situ Hybridization (FISH)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
IRF4, 6p25.3, FISH
ALCL (Anaplastic Large Cell Lymphoma)
Anaplastic Large Cell Lymphoma (ALCL)
Cutaneous ALCL (Anaplastic Large Cell Lymphoma)
ALCL (Anaplastic Large Cell Lymphoma)
Anaplastic Large Cell Lymphoma (ALCL)
Cutaneous ALCL (Anaplastic Large Cell Lymphoma)
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.
Submit only 1 of the following specimens:
Specimen Type: Lymph node
Preferred: Tissue block
Collection Instructions: Formalin-fixed, paraffin-embedded (FFPE) tumor tissue block. Include 1 hematoxylin and eosin (H and E)-stained slide.
Collection Instructions: For each probe set ordered, 2 unstained consecutive tissue sections cut at 5 microns and placed on positively charged microscope slides. Include 1 H and E-stained slide.
Forms: If not ordering electronically, complete and submit a Hematopathology/Molecular Oncology Request Form (Supply T241) 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.
Formalin-fixed paraffin-embedded tissue block or 2 consecutive unstained 5-micron thick sections placed on positive-charged microscope slides and 1 hematoxylin-and-eosin stained slide.
Note: No specimen should be rejected. If specimen not received at appropriate temperature, include note to laboratory. If questions, contact laboratory.
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
Primary cutaneous anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell lymphoproliferative disorder presenting in the skin and affecting predominantly adults with a male to female ratio of about 2:1 to 3:1. Most patients have solitary or localized tumor nodules, often with ulceration. About 20% of cases are multifocal. Regional lymph nodes may be secondarily involved.
The differential diagnosis in skin biopsies includes lymphomatoid papulosis (LyP), transformed mycosis fungoides (MF), and secondary skin involvement by systemic ALCL. All these disorders have overlapping morphologic and immunophenotypic features, making collection of a comprehensive clinical history and staging paramount. LyP typically demonstrates a chronic course with a history of waxing and waning papular skin lesions. Transformed MF requires an established diagnosis of MF. Diagnosis of systemic ALCL is based on presence of systemic disease, timing of skin versus nodal disease, with or without the presence of anaplastic lymphoma kinase (ALK) protein or ALK gene rearrangements, both of which are absent in cutaneous ALCL based on World Health Organization (WHO) criteria.
Recurrent translocations in or near the IRF4 (interferon regulatory factor 4) gene locus on 6p25.3 have been described in cutaneous ALCLs. IRF4 translocations occur in 20% to 57% of cutaneous ALCLs, and recent studies have shown high specificity for this disorder when present in skin biopsies involved by T-cell lymphoproliferative disorders. Most CD30-positive T-cell lymphoproliferative disorders are positive for the IRF4/MUM1 protein by immunohistochemistry, regardless of translocation status; thus, unlike ALK, IRF4/MUM1 immunohistochemistry is not a surrogate for testing for IRF4 translocations.
There currently are insufficient data to suggest presence of an IRF4 translocation has prognostic value in T-cell lymphoproliferative disorders. Absence of an IRF4 translocation does not exclude cutaneous ALCL. Rare instances of IRF4 translocations have been reported in LyP, transformed MF, systemic ALK-negative ALCL, and CD30-negative systemic T-cell lymphoma; therefore, testing for IRF4 translocations does not eliminate the need for, or take precedence over, collecting a thorough clinical history and staging.
IRF4 translocations are also seen in a subset of multiple myelomas and occasional B-cell lymphomas of various subtypes; however, clinical utility for demonstrating their presence in B-lineage neoplasms has not been established.
For testing for other T-cell disorders in tissues, see 89041 T-Cell Lymphoma, FISH, Tissue.
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 interpretative report will be provided.
Among cutaneous CD30-positive T-cell lymphoproliferative disorders, rearrangement of the IRF4 (interferon regulatory factor 4) gene at 6p25.3 is most closely associated with a diagnosis of cutaneous anaplastic large cell lymphoma (ALCL). However, systemic ALCL, lymphomatoid papulosis, and transformed mycosis fungoides are not excluded by this result. Furthermore, other T- and B-lineage neoplasms can demonstrate this finding. Clinical and pathologic correlation is recommended.
A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal cutoff for the IRF4 probe set.
A positive result is consistent with the diagnosis of ALCL, but is not exclusive to this disorder. Among cutaneous CD30-positive T-cell lymphoproliferative disorders, rearrangement of the IRF4 gene at 6p25.3 is most closely associated with a diagnosis of cutaneous anaplastic large cell lymphoma (ALCL). However, systemic ALCL, lymphomatoid papulosis, and transformed mycosis fungoides are not excluded by this result. Furthermore, other T- and B-lineage neoplasms can demonstrate this finding. Clinical and pathologic correlation is recommended.
A negative result suggests that an IRF4 gene rearrangement is not present, but does not exclude the diagnosis of ALCL.
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 US Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for FISH assays. Although FISH testing will not be rejected due to nonformalin fixation, results may be compromised.
Paraffin-embedded tissues that have been decalcified are generally unsuccessful for FISH analysis. The pathologist reviewing the hematoxylin-and-eosin slide may find it necessary to cancel testing.
FISH analysis was performed on 33 formalin-fixed paraffin-embedded tissue samples 8 cutaneous anaplastic large cell lymphoma (ALCL) tumors and 25 noncancerous control specimens. The normal controls were used to generate a normal cutoff for this assay. Rearrangement of IRF4 was identified in 8 of 8 (100%) cutaneous ALCL specimens.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Feldman AL, Law M, Remstein ED, et al: Recurrent translocations involving the IRF4 oncogene locus in peripheral T-cell lymphomas. Leukemia 2009;23:574-580
2. Pham-Ledard A, Prochazkova-Carlotti M, Laharanne E, et al: IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases. J Invest Dermatol 2010;130:816-825
3. Wada D, Law M, de Souza A, et al: IRF4 Translocations are specific for cutaneous anaplastic large cell lymphoma in skin biopsies involved by T-cell lymphoproliferative disorders. Mod Pathol 2009;22(suppl 1):289A (abstract 1308)
Method Description Describes how the test is performed and provides a method-specific reference
The test uses a laboratory-developed IRF4 dual-color, break-apart probe strategy. Formalin-fixed, paraffin-embedded tissues are cut at 5 microns and mounted on positive-charged glass slides. The selection of tissue and the identification of target areas on the hematoxylin and eosin (H and E)-stained slide is 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 to the appropriate target areas and 2 technologists each analyze 50 interphase nuclei each (100 total) with the results expressed as a percent 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 and its performance characteristics 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.
88271 x 2-DNA probe, each
88275-Interphase in situ hybridization, 100 to 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|
|20390||Ref Path/Phys Address||N/A|
|20400||SP Signing Pathologist:||N/A|
|20401||*Previous Report Follows*||N/A|