Previous or Related Results

Cytogenetics is not performed in a vacuum. The interpretation of chromosomal abnormalities is highly context-dependent. Before finalizing a case, the laboratory scientist must review the patient’s history and prior laboratory data. This “correlation” step is essential for distinguishing between new disease, disease progression, germline variants, and technical artifacts

Previous Cytogenetic History (Longitudinal Review)

For oncology patients (e.g., Leukemia, Myeloma), cytogenetics is used to monitor disease status over time. Comparing current results to previous reports is critical

• Identification of the Original Clone
  • Scenario: A patient with CML had a t(9;22) at diagnosis 2 years ago
  • Action: The laboratory scientist must look for that specific translocation in the current sample. Detecting even one cell with t(9;22) indicates Residual Disease
• Clonal Evolution (Disease Progression)
  • Scenario: The same CML patient now presents with a t(9;22) and a new Trisomy 8 (+8)
  • Interpretation: This is not a random finding; it represents Clonal Evolution, a sign that the disease is becoming more aggressive (Blast Crisis). The report must clearly state that the +8 is a new finding relative to the previous study
• Remission Status
  • Scenario: A patient previously had 100% abnormal cells. The current study shows 20 normal cells
  • Interpretation: This confirms Cytogenetic Remission

Family History (Constitutional Cases)

In prenatal or pediatric diagnosis, an abnormality might be de novo (new, likely pathogenic) or inherited (familial, potentially benign)

• Parental Studies
  • Scenario: A child has a small “marker” chromosome or a balanced translocation
  • Action: Review the parents’ karyotypes
  • Outcome: If a healthy parent has the exact same marker/translocation, it is likely a Familial Polymorphism: or a balanced rearrangement that doesn’t cause the child’s phenotype. If the parents are normal, the child’s defect is de novo, carrying a higher risk of pathology
• Previous Pregnancies
  • If a mother had a previous pregnancy with Trisomy 21, the recurrence risk for the current pregnancy is slightly elevated, justifying more rigorous screening

Related Molecular/Hematology Results

Cytogenetics often serves as the confirmation or structural mapper for other diagnostic tests

• FISH Correlation
  • Scenario: The interphase FISH panel detected an MLL (KMT2A) rearrangement
  • Action: The karyotype analyst must scrutinize Chromosome 11q23. Even if the banding looks subtle or blurry, the FISH result tells them where to look. The analyst will search specifically for a translocation involving 11q23 to identify the partner chromosome (e.g., t(9;11) or t(4;11))
• Microarray (CMA) Correlation
  • Scenario: Microarray detected a 5Mb gain on the short arm of Chromosome 5 (5p)
  • Action: The karyotype analyst looks for the structural mechanism. Is it an Unbalanced Translocation? A Marker Chromosome? An Insertion? The microarray provides the “what” (Gain of 5p); the karyotype provides the “how.”
• Hematopathology/Flow Cytometry
  • Scenario: Flow cytometry indicates a population of abnormal B-cells (Lambda restricted)
  • Action: The cytogeneticist focuses on lymphoid-associated abnormalities (e.g., t(14;18), t(8;14)) rather than myeloid ones. This targeted analysis increases the efficiency of finding the relevant clone

Discrepancy Analysis

What happens when results don’t match?

• FISH Positive / Karyotype Negative
  • Cause: The abnormal cells might not be dividing (low mitotic index), so the metaphases analyzed are only from the healthy cells
  • Report: “Abnormality detected by FISH but not observed in standard cytogenetics.” This highlights the limitations of the culture method
• FISH Negative / Karyotype Positive
  • Cause: The FISH probe might be too small (microdeletion) or the deletion might be outside the probe target region. Or, the karyotype abnormality might be a balanced translocation that FISH enumeration probes (designed for gains/losses) cannot detect

Summary

Reviewing previous results allows the cytogeneticist to:

1. Target the Analysis: Look specifically for known prior defects (Monitoring)
2. Determine Significance: Distinguish between familial traits and new mutations
3. Resolve Mechanisms: Use structural analysis to explain molecular findings (CMA/FISH)
4. Detect Evolution: Identify new “hits” indicating disease progression