Assisting in the diagnosis and classification of certain malignant hematological disorders in bone marrow specimens
Evaluating the prognosis in patients with certain malignant hematologic disorders
Monitoring effects of treatment
Monitoring patients in remission
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| _ML20 | Metaphases, 1-19 | No, (Bill Only) | No |
| _M25 | Metaphases, 20-25 | No, (Bill Only) | No |
| _MG25 | Metaphases, >25 | No, (Bill Only) | No |
| _STAC | Ag-Nor/CBL Stain | No, (Bill Only) | No |
This test includes a charge for cell culture of fresh specimens and professional interpretation of results. Analysis charges will be incurred for total work performed, and generally include 2 banded karyograms and the analysis of 20 metaphase cells. If no metaphase cells are available for analysis, no analysis charges will be incurred. If additional analysis work is required, additional charges may be incurred.
In addition to the cell culture without mitogens, a CpG-stimulated culture will be added and 10 additional cells will be analyzed for any specimen received from a patient age 30 or older with a reason for testing of chronic lymphocytic leukemia, small lymphocytic leukemia, lymphocytosis, Waldenstrom macroglobulinemia, or when test CLLDF / Chronic Lymphocytic Leukemia, Diagnostic FISH, Varies is ordered concurrently.
If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow.
For more information see:
-Acute Leukemias of Ambiguous Lineage Testing Algorithm
-Acute Myeloid Leukemia: Testing Algorithm
-Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
-Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
-B-Lymphoblastic Leukemia/Lymphoma Algorithm
-Bone Marrow Staging for Known or Suspected Malignant Lymphoma Algorithm
-Multiple Myeloma: Laboratory Screening
-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation
-Mast Cell Disorder: Diagnostic Algorithm, Bone Marrow
Cell Culture without Mitogens followed by Chromosome Analysis
Karyotype, Bone Marrow
This test includes a charge for cell culture of fresh specimens and professional interpretation of results. Analysis charges will be incurred for total work performed, and generally include 2 banded karyograms and the analysis of 20 metaphase cells. If no metaphase cells are available for analysis, no analysis charges will be incurred. If additional analysis work is required, additional charges may be incurred.
In addition to the cell culture without mitogens, a CpG-stimulated culture will be added and 10 additional cells will be analyzed for any specimen received from a patient age 30 or older with a reason for testing of chronic lymphocytic leukemia, small lymphocytic leukemia, lymphocytosis, Waldenstrom macroglobulinemia, or when test CLLDF / Chronic Lymphocytic Leukemia, Diagnostic FISH, Varies is ordered concurrently.
If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow.
For more information see:
-Acute Leukemias of Ambiguous Lineage Testing Algorithm
-Acute Myeloid Leukemia: Testing Algorithm
-Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
-Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
-B-Lymphoblastic Leukemia/Lymphoma Algorithm
-Bone Marrow Staging for Known or Suspected Malignant Lymphoma Algorithm
-Multiple Myeloma: Laboratory Screening
-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation
-Mast Cell Disorder: Diagnostic Algorithm, Bone Marrow
Bone Marrow
Chromosome analysis is not recommended for plasma cell neoplasms due to limited clinical utility.(1) If this test and a plasma cell FISH test (PCPDS / Plasma Cell Proliferative Disorder, High-Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow; MSMRT / Mayo Algorithmic Approach for Stratification of Myeloma and Risk-Adapted Therapy Report, Bone Marrow; or MFCDF / Myeloma High Risk with Reflex Probes, Diagnostic FISH Evaluation, Fixed Cell Pellet) are ordered concurrently, this test will be canceled. If a secondary myeloid neoplasm is suspected and both this test and a plasma cell FISH (PCPDS/MSMRT/MFCDF) are needed, contact the Cytogenetics Communication Team at 800-533-1710 before sending the specimen.
Advise Express Mail or equivalent if not on courier service.
1. A reason for testing 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.
2. A pathology and/or flow cytometry report may be requested by the laboratory to optimize testing and aid in interpretation of results.
| Question ID | Description | Answers |
|---|---|---|
| CG774 | Reason for Referral |
Container/Tube:
Preferred: Yellow top (ACD)
Acceptable: Green top (sodium 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.
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
See Specimen Required
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Bone Marrow | Ambient (preferred) | ||
| Refrigerated | |||
Assisting in the diagnosis and classification of certain malignant hematological disorders in bone marrow specimens
Evaluating the prognosis in patients with certain malignant hematologic disorders
Monitoring effects of treatment
Monitoring patients in remission
This test includes a charge for cell culture of fresh specimens and professional interpretation of results. Analysis charges will be incurred for total work performed, and generally include 2 banded karyograms and the analysis of 20 metaphase cells. If no metaphase cells are available for analysis, no analysis charges will be incurred. If additional analysis work is required, additional charges may be incurred.
In addition to the cell culture without mitogens, a CpG-stimulated culture will be added and 10 additional cells will be analyzed for any specimen received from a patient age 30 or older with a reason for testing of chronic lymphocytic leukemia, small lymphocytic leukemia, lymphocytosis, Waldenstrom macroglobulinemia, or when test CLLDF / Chronic Lymphocytic Leukemia, Diagnostic FISH, Varies is ordered concurrently.
If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow.
For more information see:
-Acute Leukemias of Ambiguous Lineage Testing Algorithm
-Acute Myeloid Leukemia: Testing Algorithm
-Acute Myeloid Leukemia: Relapsed with Previous Remission Testing Algorithm
-Acute Promyelocytic Leukemia: Guideline to Diagnosis and Follow-up
-B-Lymphoblastic Leukemia/Lymphoma Algorithm
-Bone Marrow Staging for Known or Suspected Malignant Lymphoma Algorithm
-Multiple Myeloma: Laboratory Screening
-Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation
-Mast Cell Disorder: Diagnostic Algorithm, Bone Marrow
Chromosomal abnormalities play a central role in the pathogenesis, diagnosis, and treatment monitoring of many hematologic disorders. Cytogenetic studies on bone marrow may be helpful in many malignant hematologic disorders as the observation of a chromosomally abnormal clone may be consistent with a neoplastic process.
Certain chromosome abnormalities may help classify a malignancy. As examples, the Philadelphia (Ph) chromosome, also referred to as der(22)t(9;22)(q34;q11.2), is usually indicative of chronic myeloid leukemia (CML) or acute leukemia; t(8;21)(q22;q22) defines a specific subset of patients with acute myeloid leukemia; and t(8;14)(q24.1;q32) is associated with Burkitt lymphoma.
Cytogenetic studies are also used to monitor patients with hematologic neoplasia and may identify disease progression, such as the onset of blast crisis in CML, which is often characterized by trisomy 8, isochromosome 17q, and multiple Ph chromosomes.
Conventional chromosome studies of B-cell disorders are not always successful because B lymphocytes do not proliferate well in cell culture. The agent CpG 7909 (CpG) is a synthetic oligodeoxynucleotide that binds to the Toll-like receptor 9 (present on B cells, causing B-cell activation. In the laboratory setting, CpG may be used as a mitogen to stimulate B cells in patient specimens, thus allowing identification of chromosome abnormalities. CpG stimulation reveals an abnormal karyotype in approximately 80% of patients with chronic lymphocytic leukemia, and the karyotype is complex in 20% to 25% of cases. Several studies have reported that increased genetic complexity revealed by CpG-stimulated chromosome studies confers a less favorable time to first treatment, treatment response, and overall survival.
An interpretative report will be provided.
To ensure the best interpretation, it is important to provide some clinical information to verify the appropriate type of cytogenetic study is performed.
The following factors are important when interpreting the results:
-Although the presence of an abnormal clone usually indicates a malignant neoplastic process, in rare situations, the clone may reflect a benign condition.
-The absence of an abnormal clone may be the result of specimen collection from a site that is not involved in the neoplasm or may indicate that the disorder is caused by submicroscopic abnormalities that cannot be identified by chromosome analysis.
-On rare occasions, the presence of an abnormality may be associated with a constitutional abnormality that is not related to a malignant neoplastic process. Follow-up with a medical genetics consultation is recommended.
-On occasion, bone marrow chromosome studies are unsuccessful. If clinical information has been provided, there may be a fluorescence in situ hybridization study option that could be performed.
In some cases, fluorescence in situ hybridization (FISH) studies may detect some disorders better than conventional chromosome studies:
-For plasma cell proliferative disorders such as multiple myeloma, FISH studies will detect chromosome anomalies with prognostic significance much more often than conventional chromosome studies. In this situation, PCPDS / Plasma Cell Proliferative Disorder, High-Risk with Reflex Probes, Diagnostic FISH Evaluation, Bone Marrow
is recommended.
Interfering factors:
Technical:
-Insufficient bone marrow specimen
-Use of an improper anticoagulant or improperly mixing the blood with the anticoagulant
-Clotted bone marrow specimen
-Excessive transport time
-Exposure of the specimen to extreme temperature
-Not processing the bone marrow as indicated before shipping the specimen
-Not sending the first aspirate from the patient's bone marrow collection
Biological:
-Abnormalities missed due to sampling error
-Subtle structural chromosome abnormalities may not be detected by conventional chromosome analysis
-Neoplastic cells not dividing or not present in bone marrow
1. Mellors PW, Binder M, Ketterling RH, et al. Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma. Blood Adv. 2020;4(10):2236-2244
2. Dewald GW, Ketterling RP, Wyatt WA, Stupca PJ. Cytogenetic studies in neoplastic hematologic disorders. In: McClatchey KD, ed. Clinical Laboratory Medicine. 2nd ed. Williams and Wilkens; 2002:658-685
3. Rigolin GM, Cibien F, Martinelli S, et al. Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with "normal" FISH: correlations with clinicobiological parameters. Blood. 2012;119(10):2310-2313
4. Swerdlow et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press:Lyon, 2017
A cell count is performed on the specimen to establish a plating volume. Based on the cell count, a corresponding volume of bone marrow is added to 2 culture flasks containing culture medium and incubated. In the harvest process, the cells are exposed to colcemid and hypotonic solution, and are then fixed. Metaphase cells are dropped onto microscope slides and are stained by G-banding. Other staining methods are employed as needed. Twenty metaphases are usually examined. If a clone is suspected, but not confirmed within 20 metaphases, 30 metaphases will be analyzed. Minimal evidence for the presence of an abnormal clone is defined as 2 or more metaphases with the same structural abnormality or chromosome gain (trisomy), or 3 or more metaphases lacking the same chromosome. All cells analyzed are captured using a computerized imaging system, and one or more karyograms from each clone are prepared to document the type of abnormality and to permit systematic interpretation of the anomalies.
When a specimen is received from a patient age 30 or older with a reason for testing of chronic lymphocytic leukemia, small lymphocytic lymphoma, lymphocytosis, or Waldenstrom macroglobulinemia, a CpG-stimulated culture will be added and 10 additional cells will be analyzed. Additional metaphases may be analyzed from the unstimulated or CpG-stimulated cell cultures if necessary to provide an accurate interpretation. All metaphases are captured using a computerized imaging system, and one or more karyograms from each clone are prepared to document the type of abnormality and to permit systematic interpretation of the abnormalities.(Arsham, Marilyn S., et al. eds. The AGT Cytogenetics Laboratory Manual. 4th ed. Wiley-Blackwell, 2017)
Monday through Friday
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.
88237, 88291-Tissue culture for neoplastic disorders; bone marrow, blood, Interpretation and report
88264 w/ modifier 52-Chromosome analysis with less than 20 cells (if appropriate)
88264-Chromosome analysis with 20 to 25 cells (if appropriate)
88264, 88285-Chromosome analysis with greater than 25 cells (if appropriate)
88283-Additional specialized banding technique (if appropriate)
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| CHRBM | Chromosomes, Hematologic, BM | 81861-7 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 52358 | Result Summary | 50397-9 |
| 52360 | Interpretation | 69965-2 |
| 52359 | Result | 33893-9 |
| CG774 | Reason for Referral | 42349-1 |
| 52361 | Specimen | 31208-2 |
| 52362 | Source | 31208-2 |
| 52364 | Method | 85069-3 |
| 52363 | Banding Method | 62359-5 |
| 54629 | Additional Information | 48767-8 |
| 52365 | Released By | 18771-6 |