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Test ID BLPMF B-Cell Lymphoma, Specified FISH, Varies


Ordering Guidance


This test should only be ordered if the sample is known to have a sufficient clonal B-cell population. If a flow cytometry result is available and does not identify a sufficient clonal B-cell population, this test order will be canceled, and no charges will be incurred.

 

If either the break-apart MYC or the MYC/IGH D-FISH probe set is requested in isolation, both probe sets will be performed concurrently to optimize the detection of MYC rearrangements.

 

This test should NOT be used to screen for residual B-cell lymphoma.

 

This assay detects chromosome abnormalities observed in blood or bone marrow samples of patients with B-cell lymphoma. If a paraffin-embedded tissue specimen is submitted, the test will be canceled and BLYM / B-Cell Lymphoma, FISH, Tissue will be added and performed as the appropriate test.

 

For patients with B-cell acute lymphoblastic leukemia/lymphoma (B-ALL/LBL), order either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, FISH, Varies, depending on the age of the patient.

 

For testing paraffin-embedded tissue samples from patients with B-cell lymphoblastic Lymphoma, see BLBLF / B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue.



Additional Testing Requirements


Microarray testing for Burkitt-like lymphoma with 11q aberration is available, order CMAH / Chromosomal Microarray, Hematologic Disorders, Varies.



Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


1. A list of probes requested for analysis is required. 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.



Specimen Required


Submit only 1 of the following specimens:

 

Preferred

Specimen Type: Bone marrow

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 2 to 3 mL

Collection Instructions:

1. It is preferable to send the first aspirate from the bone marrow collection.

2. Invert several times to mix bone marrow.

3. Send bone marrow in original tube. Do not aliquot.

 

Acceptable

Specimen Type: Whole blood

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood in original tube. Do not aliquot.


Useful For

Detecting, at diagnosis, common chromosome abnormalities associated with specific B-cell lymphoma subtypes using client specified FISH probes

Testing Algorithm

This test includes a charge for the probe application, analysis, and professional interpretation of results for one probe set (2 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

 

This is not intended as a panel test and the desired probes or suspected B-cell lymphoma subtype must be specified upon order. If the patient is being evaluated for known abnormalities, individual probes must be listed in the probe request field. This test is only appropriate for the following known subtypes of B-cell lymphoma:

 

Pediatric Burkitt lymphoma testing (aged 18 years or younger):

-Recommended probe request = 5'/3' MYC, MYC/IGH, MYC/IGK, MYC/IGL, 3'/5' BCL2, 3'/5' BCL6

Diffuse large B-cell, "double-hit", "triple hit" lymphoma testing:

-Recommended probe request = 5'/3' MYC, MYC/IGH, reflex with 3'/5' BCL2, 3'/5' BCL6

*If reflex is included in the probe request, break-apart BCL2 and BCL6 reflex testing would occur when a MYC disruption is observed

Follicular lymphoma testing:

-Recommended probe request = 3'/5' BCL2, 3'/5' BCL6

Mantle cell lymphoma (MCL) testing:

-Recommended probe request = CCND1/IGH, 5'/3' CCND1 as reflex

*If reflex is included in the probe request, break-apart CCND1 reflex testing would occur when an additional CCND1 FISH signal is detected to rule out a CCND1 gene disruption

Blastoid Mantle cell lymphoma testing:

-Recommended probe request = CCND1/IGH, TP53, 5'/3' MYC, MYC/IGH, 5'/3' CCND1 as reflex

*If reflex is included in the probe request, break-apart CCND1 reflex testing would occur when an additional CCND1 FISH signal is detected to rule out a CCND1 gene disruption

Splenic marginal zone lymphoma testing:

-Recommended probe request = D7Z1/7q32, TP53/D17Z1

 

See Common Chromosome Abnormalities in B-cell Lymphomas in Clinical Information for specific gene locations associated with these B-cell lymphoma subtypes.

 

If the laboratory is not provided a specific probe request or an appropriate B-cell lymphoma subtype, the following probes will be performed.

t(3q27;var) rearrangement, BCL6 break-apart

7q-, D7Z1/7q32

8q24.1 rearrangement, MYC break-apart

t(8;14)(q24.1;q32), MYC/IGH fusion

t(11;14)(q13;q32), CCND1/IGH fusion

-17/17p-, TP53/D17Z1

t(18q21;var) rearrangement, BCL2 break-apart

 

When this test and flow cytometry testing for leukemia/lymphoma are ordered concurrently, the flow cytometry result will be utilized to determine if sufficient clonal B-cells are available for FISH testing. If the result does not identify a sufficient clonal B-cell population, this FISH test order will be canceled, and no charges will be incurred. The B-cell lymphoma subtype will be used by the laboratory to determine appropriate FISH probes, if determined and applicable.

 

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 more information see Bone Marrow Staging for Known or Suspected Malignant Lymphoma Algorithm.

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

B-cell Lymphoma, Specified FISH

Specimen Type

Varies

Specimen Minimum Volume

Bone marrow: 1 mL; Whole blood: 2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Refrigerated 

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Mature B-cell lymphoma can be low grade, intermediate grade, or high grade, and the prognosis and clinical course are highly variable. Genetic abnormalities can assist diagnosis and have served as important prognostic markers in B-cell lymphomas. Fluorescence in situ hybridization (FISH) permits the detection of recurrent gene rearrangements associated with various chromosomal abnormalities in specific B-cell lymphoma subtypes (see Table).

 

Table. Common Chromosome Abnormalities in B-cell Lymphomas

Lymphoma type

Chromosome abnormality

FISH probe

Burkitt (pediatric,

≤18 years old)

8q24.1 rearrangement

5'/3' MYC

t(2;8)(p12;q24.1)

IGK/MYC

t(8;14)(q24.1;q32)

MYC/IGH

t(8;22)(q24.1;q11.2)

MYC/IGL

3q27 rearrangement

3'/5' BCL6

18q21 rearrangement

3'/5' BCL2

Diffuse large B-cell, "double-hit"

8q24.1 rearrangement

5'/3' MYC

t(8;14)(q24.1;q32)

MYC/IGH

----Reflex: t(8;22)(q24.1;q11.2)

MYC/IGL

----Reflex: t(2;8)(p12;q24.1)

IGK/MYC

----Reflex: 3q27 rearrangement

3'/5' BCL6

----Reflex: 18q21 rearrangement

3'/5' BCL2

Follicular

18q21 rearrangement

3'/5' BCL2

3q27 rearrangement

3'/5' BCL6

Mantle cell

t(11;14)(q13;q32)

CCND1/IGH

----Reflex: 11q13 rearrangement

5'/3' CCND1

Blastoid subtype only: deletion of 17p

TP53/D17Z1

Blastoid subtype only: 8q24.1 rearrangement

5'/3' MYC

Splenic marginal zone

Deletion of 7q

D7Z1/7q32

Deletion of 17p

TP53/D17Z1

Reference Values

An interpretive report will be provided.

Interpretation

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe set.

 

Detection of an abnormal clone supports a diagnosis of B-cell lymphoma. The specific abnormality detected may help to determine a specific B-cell lymphoma subtype.

 

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

Cautions

This test is not approved by the US Food and Drug Administration and is best used as an adjunct to existing clinical and pathologic information.

 

Bone marrow is the preferred sample type for this fluorescence in situ hybridization test. If bone marrow is not available, a blood specimen may be used if there are neoplastic cells in the blood specimen (as verified by a hematopathologist).

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

Clinical Reference

1. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017. WHO Classification of Tumours. Vol 2

2. King RL, McPhail ED, Meyer RG, et al. False-negative rates for MYC fluorescence in situ hybridization probes in B-cell neoplasms. Haematologica. 2019;104(6):e248-e251

3. Pophali PA, Marinelli LM, Ketterling RP, et al. High level MYC amplification in B-cell lymphomas: is it a marker of aggressive disease?. Blood Cancer J. 2020;10(1):5

Method Description

This test is performed using commercially available and laboratory-developed probes. Deletion of the 7q32 locus from chromosome 7 and the TP53 locus from chromosome 17 are detected using enumeration strategy probes. Rearrangements involving MYC, BCL2, BCL6, or CCND1 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 to detect t(2;8), t(8;14), t(8;22), and t(11;14). For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used, and results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

Day(s) Performed

Monday through Friday

Report Available

7 to 10 days

Test Classification

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.

CPT Code Information

88271 x 2, 88275, 88291-FISH Probe, Analysis, Interpretation; 1 probe set

88271 x 2, 88275-FISH Probe, Analysis; each additional probe set (if appropriate)

NY State Approved

Yes

Forms

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