Uterine cancer, also called endometrial cancer, will strike more than 40,000 U.S. women annually

A Gynecologic Oncology Group (GOG) study, headed by Cornelia Trimble, M.D. of the Johns Hopkins Kimmel Cancer Center, has revealed that pathologists who evaluate uterine biopsies disagree 60 percent of the time on whether the specimens contain cancerous cells. The authors, expected to present their findings at the 40th annual American Society of Clinical Oncology, say new standards for collecting and classifying biopsies are needed to improve the accuracy of diagnoses.

Cancer of the uterus is the most common cancer affecting the female reproductive tract in the United States. It is diagnosed from biopsied uterine or endometrial cells that indicate the presence of cancer or precancerous lesions called atypical endometrial hyperplasia (AEH).

"This study brought into sharp focus the fact that it is very difficult to make an accurate diagnosis from uterine biopsies," says Trimble, associate professor at the Johns Hopkins Kimmel Cancer Center. " Yet, women receiving a diagnosis of AEH face complete removal of their wombs through hysterectomy. So, we suggest these patients get a second opinion from a pathologist who specializes in gynecology ."

Trimble and colleagues in the national cooperative GOG set out to get a baseline estimate of the percentage of actual cancers found in hysterectomy samples of women diagnosed with AEH biopsies. The baseline, reported to be anywhere from 17 to 52 percent, would provide information needed to design studies to find non-surgical treatments for AEH that preserve fertility in young patients or eliminate the need for surgery in women with diabetes, hypertension or other complicating disorders. But, after reviewing biopsies from 289 patients classified as AEH, they were surprised to find a high degree of disagreement with the initial diagnosis of most of the biopsies.

In their review, the GOG investigators downgraded the biopsy diagnoses to "less than AEH," which denotes a range of benign disorders, in 25.6 percent of cases. They upgraded the AEH diagnosis to cancer in 29.1 percent cases, and were unable to agree on a diagnosis in 5.5 percent of the biopsies. The investigators agreed with the diagnosis of AEH in only 39.8 percent of cases. The overall baseline estimate of women who also had cancer present in their corresponding hysterectomy specimen was 42 percent.

Underscoring the level of disagreement and difficulty in making an accurate diagnosis, even with the GOG review, was the fact that cancer was found in corresponding hysterectomy specimens of 14 of 74 downgraded AEH biopsies, 45 of 115 AEH-diagnosed biopsies, 54 of 84 AEH specimens upgraded to cancer, and 10 of 16 cases where there was no agreement.

"We will be looking at these data more closely to determine why there was such disagreement in the diagnosis and find a better system for classifying and grading these biopsies, including using improvements in molecular markers to help identify better ways to diagnose uterine cancer," says Trimble.

Although guidelines for distinguishing benign endometrial biopsies from AEH and cancer have been accepted by the World Health Organization and Society of Gynecologic Pathologists, Trimble and her colleagues noted that the classification system has not undergone the same rigorous evaluation as other lesions, such as cervical cancer. Trimble and the GOG investigators are developing more precise classification guidelines.

Uterine cancer, also called endometrial cancer, will strike more than 40,000 U.S. women annually, and kills 7,090. The most common identifiable symptom is irregular bleeding.