Correspondence

DNA Testing to Refute a Diagnosis of Cancer

N Engl J Med 1997; 337:1245-1247October 23, 1997

Article

To the Editor:

The use of DNA testing in forensics has been widely publicized. We used DNA testing to determine that a pathological diagnosis of cancer was based on extraneous tissue and thereby avoided unnecessary treatment. A 44-year-old woman underwent a uterine myomectomy and had postoperative complications resulting in ascites and right pleural effusion two weeks later. The pleural effusion filled the right chest cavity and rapidly recurred after thoracentesis. Thoracoscopy was performed for pleurodesis. Pleural biopsy showed multiple fragments of mesothelial-cell proliferation and a single, isolated, 1-mm fragment of adenocarcinoma (Figure 1AFigure 1DNA Testing to Refute a Diagnosis of Cancer. and Figure 1B). The serum concentration of CA-125 was 500 kU per liter. The patient was transferred to our hospital, where upper gastrointestinal endoscopy was negative. The ovaries were normal on transvaginal ultrasonography. Diagnostic laparoscopy recovered 800 ml of ascites that contained no malignant cells. No intraperitoneal abnormality was seen. Blind biopsies of the peritoneum and diaphragms were negative. Three weeks after the initial surgery the serum concentration of CA-125 had fallen to 254 kU per liter. Since we could not identify a primary tumor, we decided to confirm the origin of the malignant tissue. The focus of cancer was dissected from the paraffin block and submitted, along with a sample of the patient's blood, to Cellmark Diagnostics (Germantown, Md.). DNA was isolated from the two specimens and amplified by polymerase chain reaction (PCR) for testing with the AmpliType PM+DQA1 PCR Amplification and Typing Kit. On the basis of DNA typing the patient was ruled out as the source of the DNA extracted from the paraffin block (Figure 1C). Within two months of surgery the CA-125 concentration fell to normal. Left hydronephrosis developed, and the patient was found to have had her left ureter severed during the uterine myomectomy.

Extraneous tissue was found in a large series to occur in 0.6 to 2.9 percent of surgical specimens.1 In our case, multiple sections from the paraffin block contained the focus of cancer, meaning that the cancer had been embedded as part of the surgical specimen. Gephardt and Zarbo1 found that in 28 percent of their cases the extraneous tissue was within the paraffin block and not the result of contamination of a single slide that occurred during cutting and mounting of a histologic section. The extraneous malignant tissue was introduced into the biopsy sample either during transfer of the tissue to a plastic cassette or during fixation, when numerous tissue cassettes share a common fixing bath. Endoscopic surgical techniques and needle biopsies retrieve small specimens that can be lost in handling or even escape the cassette and enter another cassette during fixation. To contain small specimens, filter papers or tea bags should be routinely used in all pathology laboratories.1 However, in cases in which the histologic diagnosis of cancer depends on small tissue fragments and is inconsistent with the clinical presentation, DNA testing may be helpful. The cost of the DNA testing was $1,850. This expenditure averted further clinical testing and the need for anticancer treatment.

Edward P. Gelmann, M.D.
Ernest Lack, M.D.
Georgetown University School of Medicine, Washington, DC 20007

1 References

1. 1

   Gephardt GN, Zarbo RJ. Extraneous tissue in surgical pathology: a College of American Pathologists Q-Probes study of 275 laboratories. Arch Pathol Lab Med 1996;120:1009-1014
   Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Robert E. Wenk. (1999) Risk investigations involving genetic identification. Journal of Healthcare Risk Management 19:1, 28-35
   CrossRef