Comparison of polymerase chain reaction, DNA hybridization, and histology with viral culture to detect cytomegalovirus in immunosuppressed patients.

Formalin-fixed, paraffin-embedded lung tissue from 34 autopsies and eight open-lung biopsies of bone marrow transplant recipients was analyzed for cytomegalovirus (CMV) infection. The cases were studied by the polymerase chain reaction (PCR), in situ DNA hybridization, and histologic examination. The results were compared with viral culture for CMV taken at the time of biopsy or autopsy. In the autopsy series, hybridization and histology identified CMV in 15% of the cases, whereas PCR detected CMV in 24% of the cases. In the open-lung biopsy cases, both PCR and hybridization were found to be equivalent to culture in detecting CMV. Histology was less sensitive, with the molecular biology methods detecting CMV in 50% of the lung biopsies while histologic examination identified only 25%. Specificity was high (100%) since CMV was not detected in any culture-negative case by either PCR or hybridization. However, PCR, hybridization, and histology failed to identify CMV in three known culture-positive autopsy cases. Overall, PCR and hybridization were found to be more sensitive than histology, and PCR was more sensitive than hybridization for the detection of CMV. The advantage of high sensitivity and specificity combined with more rapid diagnosis (24 to 48 h) compared with viral culture (average, 16 days in this study) makes the molecular biology methods useful adjuncts to histology for detection of CMV in formalin-fixed, paraffin-embedded tissue.