Laboratory Quality Failure: Discordant Melanoma FISH Results
A dermatopathology laboratory performs a 4-probe FISH assay for ambiguous melanocytic tumors. Over 3 months, 18 cases are run; 4 show signal patterns that the technologist calls positive, but the pathologist notes that 2 of these had weak signals and 1 had high background. A review of records shows the probe lot was changed mid-period and no validation was documented for the new lot. The laboratory director asks for a corrective action plan.
1. What quality failure is present, and what immediate action is needed?
Read the worked answer
The failure is use of a new probe lot without documented validation, plus subjective interpretation of weak or high-background signals. Immediate action: stop reporting affected cases, review the 18 cases (especially the 4 positives), and repeat or re-interpret with validated reagents. Notify the director and document the review. Cases should not be finalized until interpretation criteria and reagent validation are confirmed.
2. What should the corrective action plan include for validation and interpretation?
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The plan should include validation of each new probe lot against known positive and negative controls with documented acceptance criteria; standardized signal-quality criteria (minimum signal intensity, background thresholds, number of cells scored); blinded re-review of discordant cases; and competency assessment for technologists and pathologists. It should also include a policy for rejecting runs with poor signal quality and a mechanism for documenting lot changes. CAP/CLIA requirements for analytic validation and ongoing proficiency should be referenced.
3. How would you communicate the issue to clinicians and prevent recurrence?
Read the worked answer
Communicate through amended reports or addenda for affected cases, stating the reason for re-review and the final interpretation. Use a nonpunitive root-cause approach, track the corrective action to completion, and add a checklist item for lot validation before use. Audit subsequent FISH runs for signal quality and concordance. The goal is transparency with clinicians and a documented system that prevents unvalidated reagents from entering the workflow.