Test Id : MFCDF

This test includes a charge for the probe application, analysis, and professional interpretation of results for 3 probe sets (6 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

This test is designed for diagnostic bone marrow specimens from patients with multiple myeloma, or other plasma cell proliferative disorders, when either a fixed cell pellet or a bone marrow sample exceeding 96 hours post-collection is available. Best results are obtained when the bone marrow demonstrates at least 20% involvement by a plasma cell proliferative disorder.

This test is performed using either the diagnostic or follow-up analysis algorithm.

The diagnostic high-risk myeloma FISH panel includes testing for the following abnormalities using the FISH probes listed:

1p deletion/1q gain, CDKN2C/1q22 probe set

t(14q32;var) or IGH rearrangement, IGH break-apart probe set

-17/17p-, TP53/D17Z1 probe set

If an IGH rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner using the FISH probes listed:

t(4;14)(p16.3;q32) IGH::FGFR3 fusion, FGFR3/IGH probe set

t(11;14)(q13;q32) or IGH::CCND1 fusion, CCND1/IGH probe set

t(14;16)(q32;q23) IGH::MAF fusion, IGH/MAF probe set

t(14;20)(q32;q12) IGH::MAFB fusion, IGH/MAFB probe set

Use of the follow-up analysis testing algorithm is determined by the results of either previous MFCDF / Myeloma, High Risk with Reflex Probes, Diagnostic FISH Evaluation, Fixed Cell Pellet, PCPDS / Plasma Cell Proliferative Disorder, High Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow or MPCDS / mSMART, Plasma Cell Proliferative Disorder, FISH, Bone Marrow testing reported by this laboratory.

The follow-up high-risk myeloma FISH panel includes testing for the following abnormalities using the FISH probes listed:

1p deletion/1q gain, CDKN2C/1q22 probe set

t(8q24.21;var) or MYC rearrangement, MYC break-apart probe set

-17/17p-, TP53/D17Z1 probe set

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

For the most complete genetic evaluation on fresh bone marrow specimens, order MSMRT/ Mayo Algorithmic Approach for Stratification of Myeloma and Risk-Adapted Therapy Report, Bone Marrow.

For evaluation of high-risk abnormalities, with reflex probes, on fresh bone marrow specimens that will be received within 96 hours of collection, order PCPDS / Plasma Cell Proliferative Disorder, High Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow. If the specimen received for this test is within 96 hours of collection, this test will be canceled and automatically reordered by the laboratory as PCPDS.

For testing paraffin-embedded tissue specimens from patients with a plasma cell disorder, order PLASF / Plasma Cell Proliferative Disorder, FISH, Tissue. If the specimen received for this test is paraffin-embedded, this test will be canceled and automatically reordered by the laboratory as PLASF.

Fresh bone marrow is only acceptable specimen for this test if the specimen will be received 96 hours or more post-collection.

Advise Express Mail or equivalent if not on courier service.

1. A list of probes requested for analysis is required if select probes are necessary or if the patient is being tracked for known abnormalities. Probes available for this test are listed in the Testing Algorithm section.

2. A reason for testing must be provided. If this information is not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

3. A flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

Container/Tube: Sterile container

Specimen Volume: 1 Fixed cell pellet

Collection Instructions: Place specimen in a sterile container with a 3:1 methanol:glacial acetic acid (or similar) fixative.

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Detecting, at diagnosis, recurrent high-risk common chromosome abnormalities associated multiple myeloma or other plasma cell proliferative disorders, when fresh bone marrow is unavailable, using a laboratory-designated probe set algorithm

Evaluating specimens in which the bone marrow is past 96 hours from collection

This test should not be used to track the progression of disease

This test includes a charge for the probe application, analysis, and professional interpretation of results for 3 probe sets (6 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

This test is designed for diagnostic bone marrow specimens from patients with multiple myeloma, or other plasma cell proliferative disorders, when either a fixed cell pellet or a bone marrow sample exceeding 96 hours post-collection is available. Best results are obtained when the bone marrow demonstrates at least 20% involvement by a plasma cell proliferative disorder.

This test is performed using either the diagnostic or follow-up analysis algorithm.

The diagnostic high-risk myeloma FISH panel includes testing for the following abnormalities using the FISH probes listed:

1p deletion/1q gain, CDKN2C/1q22 probe set

t(14q32;var) or IGH rearrangement, IGH break-apart probe set

-17/17p-, TP53/D17Z1 probe set

If an IGH rearrangement is identified, appropriate reflex testing will be performed in an attempt to identify the translocation partner using the FISH probes listed:

t(4;14)(p16.3;q32) IGH::FGFR3 fusion, FGFR3/IGH probe set

t(11;14)(q13;q32) or IGH::CCND1 fusion, CCND1/IGH probe set

t(14;16)(q32;q23) IGH::MAF fusion, IGH/MAF probe set

t(14;20)(q32;q12) IGH::MAFB fusion, IGH/MAFB probe set

Use of the follow-up analysis testing algorithm is determined by the results of either previous MFCDF / Myeloma, High Risk with Reflex Probes, Diagnostic FISH Evaluation, Fixed Cell Pellet, PCPDS / Plasma Cell Proliferative Disorder, High Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow or MPCDS / mSMART, Plasma Cell Proliferative Disorder, FISH, Bone Marrow testing reported by this laboratory.

The follow-up high-risk myeloma FISH panel includes testing for the following abnormalities using the FISH probes listed:

1p deletion/1q gain, CDKN2C/1q22 probe set

t(8q24.21;var) or MYC rearrangement, MYC break-apart probe set

-17/17p-, TP53/D17Z1 probe set

Appropriate ancillary probes may be performed at consultant discretion to render comprehensive assessment. Any additional probes will have the results included within the final report and will be performed at an additional charge.

Multiple myeloma is a hematologic neoplasm that generally originates in the bone marrow and develops from malignant plasma cells. There are 4 main categories of plasma cell proliferative disorders: monoclonal gammopathy of undetermined significance (MGUS), monoclonal immunoglobulin deposition diseases (amyloidosis), plasmacytoma, and multiple myeloma. MGUS, which occurs in 3% to 4% of individuals older than 50 years, represents the identification of an asymptomatic monoclonal protein, yet approximately 1% per year will progress to multiple myeloma. Amyloidosis represents a rare group of deposition disorders including primary amyloidosis vs. light chain and heavy chain disease. Plasmacytomas represent isolated collections of bone or extramedullary plasma cells with a risk for development of multiple myeloma. Generalized bone pain, anemia, limb numbness, or weakness, symptoms of hypercalcemia, and recurrent infections are all symptoms that may indicate multiple myeloma.

As myeloma progresses, the malignant plasma cells interfere with normal blood product formation in the bone marrow resulting in anemia and leukopenia. Myeloma also causes an overstimulation of osteoclasts, causing excessive breakdown of bone tissue without the normal corresponding bone formation. These bone lesions are seen in approximately 66% of myeloma patients. In advanced disease, bone loss may reach a degree where the patient suffers fractures easily.

Multiple myeloma is increasingly recognized as a disease characterized by marked cytogenetic, molecular, and proliferative heterogeneity. This heterogeneity is manifested clinically by varying degrees of disease aggressiveness. Multiple myeloma patients with more aggressive disease experience suboptimal responses to some therapeutic approaches; therefore, identifying these patients is critically important for selecting appropriate treatment options.

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 any given probe set.

The absence of an abnormal clone does not rule out the presence of a plasma cell clone or another neoplastic disorder.

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.

If no fluorescence in situ hybridization (FISH) signals are observed post-hybridization, the case will be released indicating a lack of FISH results.

1. Swerdlow S, Campo E, Harris NL, et al, eds: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press; 2017

2. Kumar SK, Rajkumar SV. The multiple myelomas-current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018;15(7):409-421. doi:10.1038/s41571-018-0018-y

3. Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015;125(20):3069-3075. doi:10.1182/blood-2014-09-568899

4. Muchtar E, Dispenzieri A, Kumar S, et al. Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category. Leukemia. 2017;31(7);1562-1569. doi:10.1038/leu.2016.369

5. Lakshman A, Paul S, Rajkumar SV, et al. Prognostic significance of interphase FISH in monoclonal gammopathy of undetermined significance. Leukemia. 2018;32(8);1811-1815. doi:10.1038/s41375-018-0030-3

6. Bochtler T, Hegenbart U, Kunz C, et al. Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study. Blood. 2016;128(4):594-602. doi:10.1182/blood-2015-10-7

7. Treatment guidelines: multiple myeloma. mSMART 3.0. Accessed March 3, 2025. Available  www.msmart.org/mm-treatment-guidelines

This test is performed using commercially available and laboratory-developed probes. Deletion of the TP53 locus from chromosome 17 or monosomy 17 and deletion of the CDKN2C locus or gain of the 1q22 locus are detected using enumeration strategy probes. Rearrangements involving IGH and MYC are detected using dual-color break-apart (BAP) strategy probes. Dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe sets are used when a rearrangements of the IGH gene is detected. For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. All results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

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This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

88271x6, 88275x3, 88291 x1-FISH Probe, Analysis, Interpretation; 3 probe sets

88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)