DNA ???Fingerprint??? Evaluation of Clinical Specimen Contamination

A young female patient was identified by cytologic diagnosis as showing high-grade squamous intraepithelial lesion (HSIL) and glandular dysplasia and underwent a cervical cone biopsy. A 1.3-mm microinvasive adenocarcinoma was identified that extended to the margins. An abdominal hysterectomy was performed and showed no residual disease. The pelvic-wash cell block, however, showed a tissue fragment that was interpreted as metastatic adenocarcinoma. Upon review of this fragment, concerns were raised that the cells did not reflect the histology of the original malignant biopsy specimen and that cancer was not identified in the hysterectomy specimen. The possibility was raised that the malignant cells represented contamination of the specimen with malignant cells from a different patient. As this quandary presented an obstacle to staging and the treatment plan, the specimen was subjected to molecular analysis to evaluate the possibility of tissue contamination. A representation from the minor fragment containing the atypical cells was separately captured by laser capture microdissection and compared with an independent tissue specimen from the same patient. Genomic DNA was extracted from the specimens and subjected to analysis of a variety of different polymorphic microsatellite markers. All markers showed identity of the alleles from separate specimens. The results confirmed that the minor fragment was from the correct patient and not a contaminant. This case illustrates the use of forensic DNA identification techniques in cytopathology and serves as a focus for review of DNA “fingerprinting” applications to laboratory medicine.