Introduction:
Traditional cytogenetic analysis to identify chromosome abnormalities associated with hematologic malignancies can also incidentally reveal abnormal constitutional karyotypes. Examples of cytogenetic abnormalities that might raise suspicion for constitutional origin when observed in all cells examined may include an apparently balanced structural rearrangement that is not known to be associated with hematologic malignancies or an aneuploidy involving the sex chromosomes. The identification of an abnormality as potentially reflective of the constitutional chromosome complement rather than a clonal process is important for the correct interpretation of the karyotype related to the patient’s hematologic malignancy. This information can also hold significant value for the patient and their relatives that is unrelated to the patient’s cancer, such as informing them about the possible reproductive outcomes associated with the abnormal segregation of chromosomes involved by a balanced structural rearrangement. It is therefore necessary for the clinical test report to clearly communicate the suspicion of a constitutional chromosome abnormality and to provide the patient and their clinicians with options for follow-up testing to confirm or refute a constitutional origin. Factors that might influence the amount of time between reporting the suspected constitutional abnormality and the receipt of a sample for follow-up constitutional cytogenetic analysis, or the patient’s decision whether to pursue this follow-up testing at all, may include the status of treatment for their hematologic malignancy, their age and life stage, and the type of chromosome abnormality detected. We completed a review of the cytogenetic testing for hematologic malignancies performed in our academic cytogenetics laboratory to investigate the rate of follow-up constitutional cytogenetic analysis when it was recommended in the clinical test report.

 

Methods:
Our cytogenetics laboratory internal database was queried for cancer cytogenetic test reports signed out over a three-year period that included a recommendation for follow-up constitutional cytogenetic analysis due to the identification of an abnormality suspicious for constitutional origin.  For each case it was determined whether follow-up testing was completed, and if so, whether an abnormal constitutional karyotype was confirmed. Patients with known constitutional karyotype abnormalities were excluded from this study.

 

Results:
During the three-year study period, cytogenetic test reports for 25 patients were signed out with a recommendation for constitutional follow-up testing on a peripheral blood sample to be taken during a period when the patient is not undergoing treatment. The suspicious cytogenetic abnormalities included 5 apparently balanced reciprocal translocations, 3 Robertsonian translocations, 5 pericentric and 6 paracentric inversions, 4 sex chromosome aneuploidies, and 2 small supernumerary ring chromosomes. A peripheral blood sample for G-banded karyotype analysis of phytohemagglutinin (PHA)-stimulated lymphocytes was subsequently received for 6 of these patients, and 5 of the abnormalities were confirmed to be constitutional. These included a paracentric inversion in a 46-year-old male with a plasma cell neoplasm, a reciprocal translocation in a 50-year-old female with a plasma cell neoplasm, a reciprocal translocation in a 6-year-old female with B-cell acute lymphoblastic leukemia, a Robertsonian translocation in a 26-year-old female with follicular lymphoma, and a Robertsonian translocation in a 57-year-old male with B-cell acute lymphoblastic leukemia. The single abnormality that was not confirmed to be constitutional was a sex chromosome aneuploidy observed in a subset of cells in a lymph node biopsy sample from a 27-year-old male whose final pathology report noted reactive lymphoid hyperplasia without evidence of lymphoma.

Conclusion:
The recognition of chromosome abnormalities as potentially constitutional rather than related to a clonal process during cancer cytogenetic testing is essential for the correct interpretation of results. Additionally, this creates an opportunity for the patient to learn information that may have relevance for their self and their relatives. Patients with incidentally detected abnormal constitutional karyotypes should be offered genetic counseling.