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HelpTest ID BLBLF B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue
Ordering Guidance
This test does not include a pathology consult. If a pathology consultation is requested, PATHC / Pathology Consultation should be ordered and the appropriate fluorescence in situ hybridization (FISH) test will be ordered and performed at an additional charge.
For testing non-paraffin bone marrow or blood samples from patients with B-cell acute lymphoblastic leukemia/lymphoma, order either BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies or BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies, depending on the patient's age. If non-paraffin bone marrow or blood sample is received for this test, it will be canceled, and either BALPF or BALAF, depending on patient's age, will be added and performed as the appropriate test.
For patients with B-cell lymphoma, order BLYM / B-Cell Lymphoma, FISH, Tissue.
Shipping Instructions
Advise Express Mail or equivalent if not on courier service.
Necessary Information
A reason for testing and pathology report are required for testing to be performed. Send information with specimen. Acceptable pathology reports include working drafts, preliminary pathology, or surgical pathology reports. The laboratory will not reject testing if this information is not provided; however. appropriate testing and interpretation may be compromised or delayed. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.
Specimen Required
Submit only 1 of the following specimens:
Specimen Type: Tissue
Preferred: Tissue block
Collection Instructions: Submit a formalin-fixed, paraffin-embedded tumor tissue block. Blocks prepared with alternative fixation methods may be acceptable; provide fixation method used.
Additional Information:
1. Paraffin-embedded specimens can be from any anatomic location (skin, soft tissue, lymph node, etc).
2. Bone specimens that have been decalcified will be attempted for testing, but the success rate is approximately 50%.
Acceptable: Tissue slides
Collection Instructions: 20 Consecutive, unstained, 5-micron thick sections placed on positively charged slides and 1 hematoxylin and eosin-stained slide.
Forms
If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
Secondary ID
609451Useful For
Detecting a neoplastic clone in paraffin-embedded specimens associated with the common chromosome abnormalities seen in patients with B-cell lymphoblastic leukemia/lymphoma
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| _IL25 | Interphases, <25 | No, (Bill Only) | No |
| _I099 | Interphases, 25-99 | No, (Bill Only) | No |
| _I300 | Interphases, >=100 | No, (Bill Only) | No |
| _PADD | Probe, +1 | No, (Bill Only) | No |
| _PB02 | Probe, +2 | No, (Bill Only) | No |
| _PB03 | Probe, +3 | No, (Bill Only) | No |
| _PBCT | Probe, +2 | No, (Bill Only) | No |
Testing Algorithm
This test includes a charge for application of the first probe set (2 fluorescence in situ hybridization [FISH] probes) and professional interpretation of results. Additional charges will be incurred for all reflex probes 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 FISH test allows different combinations of probes to be utilized based on the patient's age and clinical question, including the standard (diagnostic) B-cell lymphoblastic lymphoma (B-LBL) FISH panel and the individual B-LBL FISH probes (per client request).
The FISH panel for patients 30 years and younger includes testing for the following abnormalities using the FISH probes listed:
+9/9p-, CDKN2A/D9Z1
t(9;22) BCR/ABL1
11q23 rearrangement, MLL (KMT2A) break-apart
-17/17p-, TP53/D17Z1
t(1;19)(q23;p13), PBX1/TCF3
Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22), ETV6/RUNX1 fusion and iAMP21
14q32 rearrangement, IGH break-apart
8q24.1 rearrangement, MYC break-apart
If the initial FISH panel demonstrates normal or nonclassical abnormalities, the Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel will be performed.
The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
The initial FISH panel for patients older than 30 years of age includes testing for the following abnormalities using the FISH probes listed:
t(9;22) BCR/ABL1
If BCR/ABL1 fusion is not observed, the Ph-like ALL panel will be performed. The Ph-like ALL panel includes testing for the following kinase activating chromosome abnormalities, using the FISH probes listed below:
1q25 rearrangement, ABL2 break-apart
5q32 rearrangement, PDGFRB break-apart
9p24.1 rearrangement, JAK2 break-apart
9q34 rearrangement, ABL1 break-apart
If the previous FISH probe sets demonstrate normal or nonclassical abnormalities, the following probe sets will be performed:
t(1;19)(q23;p13), PBX1/TCF3 fusion
Hyperdiploidy, +4,+10,+17: D4Z1/D10Z1/D17Z1
t(12;21)(p13;q22), ETV6/RUNX1 fusion and iAMP21
14q32 rearrangement, IGH break-apart
11q23 rearrangement, MLL (KMT2A) break-apart
When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of:
t(4;11)(q21;q23) AFF1/MLL
t(6;11)(q27;q23) MLLT4(AFDN)/MLL
t(9;11)(p22;q23) MLLT3/MLL
t(10;11)(p12;q23) MLLT10/MLL
t(11;19)(q23;p13.1) MLL/ELL
t(11;19)(q23;p13.3) MLL/MLLT1.
In the absence of BCR/ABL1 fusion, when an extra ABL1 signal is identified, reflex testing will be performed using the ABL1 break-apart probe set to evaluate for the presence or absence of an ABL1 rearrangement.
In the absence of ETV6/RUNX1 fusion, when an extra ETV6 signal is identified, reflex testing will be performed using the ETV6 break-apart probe set to evaluate for the presence or absence of an ETV6 rearrangement.
If a MYC rearrangement is identified, both the BCL2 and BCL6 probe sets will be performed.
For more information, see B-Lymphoblastic Leukemia/Lymphoma Algorithm.
Special Instructions
Method Name
Fluorescence In Situ Hybridization (FISH)
Reporting Name
B-Lymphoblastic Leuk/Lymph, FISH,TsSpecimen Type
TissueSpecimen Minimum Volume
Fifteen consecutive, unstained, 5-micron thick sections placed on positively charged slides, and 1 hematoxylin and eosin-stained slide.
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Tissue | Ambient (preferred) | |
| Refrigerated | ||
Clinical Information
In the United States, the incidence of B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is roughly 6000 new cases per year or approximately 1 in 50,000 individuals. B-ALL/LBL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. It has a peak incidence at 2 to 5 years of age. This incidence decreases with age before increasing again at around 50 years of age. B-ALL/LBL is slightly more common in male patients than female patients. There is also an increased incidence of B-ALL/LBL in individuals with genetic conditions such as Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for B-ALL/LBL in children is approximately 90%, and about 45% to 60% of adults have long-term disease-free survival. Of note, CRLF2/IGH rearrangements are more commonly observed in patients with Down syndrome or of Hispanic descent.
Specific cytogenetic abnormalities are identified in the majority of cases of B-ALL/LBL, either by conventional chromosome studies or fluorescence in situ hybridization studies. Each of the genetic subgroups is important to detect and can be critical prognostic markers. For example, a decision for early transplantation may be made if t(9;22)(q34;q11.2), KMT2A rearrangement, iAMP21, or a hypodiploid clone is identified. In contrast, if the ETV6/RUNX1 fusion or hyperdiploidy is identified, the patient has a more favorable prognosis and transplantation is rarely initially considered.
A newly recognized World Health Organization entity called BCR-ABL1-like ALL, also known as Philadelphia chromosome-like acute lymphoblastic leukemia, is increasing in importance due to the poor prognosis seen in pediatric, adolescent, and young adult ALL. Common features of this entity involve rearrangements with tyrosine kinase genes involving the following genes: ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8, as well as deletions involving IKZF1. Patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies when rearrangements involving these specific gene regions have been identified.
Evaluation of the MYC gene region is included in all diagnostic B-ALL panels to evaluate for Burkitt lymphoma. If a positive result is obtained, additional testing for the BCL2 and BCL6 gene regions will be performed.
Per National Comprehensive Cancer Network guidelines, a combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients with B-ALL/LBL.
Table. Common Chromosome Abnormalities in B-cell Acute Lymphoblastic Leukemia/Lymphoma
|
Leukemia type |
Cytogenetic change |
Typical demographic |
Risk category |
|
B-cell acute lymphoblastic leukemia |
t(12;21)(p13;q22), ETV6/RUNX1 |
Pediatric |
Favorable |
|
Hyperdiploidy |
Pediatric |
Favorable |
|
|
t(1;19)(q23;p13.3), PBX1/TCF3 |
Pediatric |
Intermediate to favorable |
|
|
t(9;22)(q34;q11.2), BCR/ABL1 |
All ages |
Unfavorable |
|
|
iAMP21, RUNX1 |
Pediatric |
Unfavorable |
|
|
del(9p), CDKN2A |
All ages |
Unknown |
|
|
t(11q23;var), MLL |
All ages |
Unfavorable |
|
|
t(4;11)(q21;q23), AFF1/MLL |
All ages |
Unfavorable |
|
|
t(6;11)(q27;q23), MLLT4(AFDN)/MLL |
All ages |
Unfavorable |
|
|
t(9;11)(p22;q23), MLLT3/MLL |
All ages |
Unfavorable |
|
|
t(10;11)(p12;q23), MLLT10/MLL |
All ages |
Unfavorable |
|
|
t(11;19)(q23;p13.1), MLL/ELL |
All ages |
Unfavorable |
|
|
t(11;19)(q23;p13.3), MLL/MLLT1 |
All ages |
Unfavorable |
|
|
t(14q32;var), IGH |
All ages |
Variable |
|
|
-17/17p-, TP53 |
All ages |
Unfavorable |
|
|
t(8q24.1;var), MYC |
Pediatric/ adolescent/ young adult |
||
|
Complex karyotype (≥4 abnormalities) |
Adult |
Unfavorable |
|
|
Low hypodiploidy/near triploidy |
Adult |
Unfavorable |
|
|
Near-haploid/hypodiploid |
All ages |
Unfavorable |
|
|
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) |
t(1q25;var), ABL2 |
Pediatric/ adolescent/ young adult |
Unfavorable |
|
t(5q32;var), PDGFRB |
|||
|
t(9p24.1;var), JAK2 |
|||
|
t(9q34;var), ABL1 |
Reference Values
An interpretive report will be provided.
Cautions
This test is not approved by the US Food and Drug Administration, and it is best used as an adjunct to clinical and pathologic information.
Fixatives other than formalin (eg, Prefer, Bouin's) may not be successful for fluorescence in situ hybridization (FISH) assays. Although FISH testing will not be rejected due to non-formalin fixation, results may be compromised.
Paraffin-embedded tissues that have been decalcified may be unsuccessful for FISH analysis.
FISH studies will be attempted if sufficient tumor is present for analysis. The pathologist reviewing the hematoxylin and eosin-stained slide may find it necessary to cancel testing. If no FISH signals are observed post-hybridization, the case will be released indicating a lack of FISH results.
Day(s) Performed
Monday through Friday
Report Available
7 to 10 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
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, 88291-DNA probe, each (first probe set), interpretation and report
88271 x 2-DNA probe, each; each additional probe set (if appropriate)
88271-DNA probe, each; coverage for sets containing 3 probes (if appropriate)
88271 x 2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)
88271 x 3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)
88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)
88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)
88275-Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)