CASE: Apprehension over a chance of cancer
She was frightened of the ovarian cyst that her gyn detected during an annual exam, thinking that he might find that she had ovarian cancer. She was only 45 years old, after all, dreaming of many more birthdays, desiring to be there to see her children marry, hoping to play with her grandchildren.
Now, she had to shoulder the anxiety of wondering what might be discovered at surgery. Well, did she have ovarian cancer? Was she going to die far, far too young?
According to the American Cancer Society, approximately 21,550 new cases of ovarian cancer were diagnosed last year and 14,600 women died of the disease. In fact, in the United States, ovarian cancer is the most common cause of death from a gynecologic malignancy.
To our frustration, ovarian cancer typically isn’t diagnosed until it has reached an advanced stage. What we’ve needed, and what would greatly advance women’s health, are new tests to identify ovarian cancer at an early stage. That dream hasn’t been realized, but we can be pleased that a new test for the glycoprotein human epididymis protein 4, or HE4, will improve our ability to properly treat women in whom ovarian cancer has been diagnosed.
Snapshot of the new test
HE4 is expressed in normal male and female reproductive tract epithelium and in pulmonary epithelium. Its biologic function hasn’t been fully characterized, but it may be an inhibitor of trypsin.
A team of researchers led by Leroy Hood reported in 1999 that HE4 was over-expressed in ovarian cancer tissues.1 Their discovery translated to development* of an ELISA blood test for HE4 that has value in detecting and managing ovarian cancer.
HE4 is overexpressed in:
- approximately 90% of women who have serous ovarian cancer
- 99% of women who have endometrioid ovarian cancer
- 50% of women who have clear-cell cancer.
- mucinous and germ-cell ovarian cancers do not over-express HE4. The normal range of circulating HE4 is ≤150 picomoles/L, or picomolar (pM). In one study, the mean serum HE4 level in healthy control women was 41 pM; in those who had ovarian cancer, 1,125 pM.2
*By Fujirebio Diagnostics. The test is available through Quest Diagnostics.
Recurrence and progression of ovarian Ca monitored with HE4
The assay for HE4 has been approved by the US Food and Drug Administration to aid in monitoring the recurrence and the progression of epithelial ovarian cancer. The test is not FDA-approved for making a diagnosis of ovarian cancer.
The National Comprehensive Cancer Network recommends that, for women who have ovarian cancer and an elevated level of CA 125 at the time of their diagnosis, the level of CA 125 be measured before each cycle of chemotherapy. This approach helps to ensure that disease activity is accurately monitored and progression is detected quickly—enabling the oncologist to switch as necessary to a more effective regimen.
Measuring both CA 125 and HE4 before each cycle of chemotherapy likely improves the accuracy of the determination of a patient’s true clinical status. An increase of 25% or more across sequential HE4 measurements suggests recurrence or progression of disease. Conversely, a stable HE4 level across sequential measurements is reassuring.
Determining the presence of a malignancy is a major goal in the preoperative evaluation of a woman who has a pelvic mass. As I noted, referring a patient in whom you suspect ovarian cancer or pelvic malignancy to a specialty center for care increases her chance of survival.
Pelvic US is critical and the platelet count is useful in the preoperative evaluation of a pelvic mass. Here’s how to apply these studies.
Sonographic findings in an ovarian cyst that raise the risk of an ovarian malignancy include:
- solid tumor with irregular borders
- detection of four or more papillary structures in the cyst or tumor
- ovarian cyst diameter greater than 10 cm
- Doppler demonstration of significant blood flow into the cyst or tumor.1
US findings that suggest the ovarian cyst is benign include:
- unilocular cyst
- no solid cyst component greater than 7 mm in diameter
- smooth cyst surface
- no significant blood flow into the cyst on Doppler imaging.1
The platelet count is routinely available to you preoperatively because it is automatically reported as part of a complete blood count.
In a woman who has a pelvic mass, a preop platelet count of ≥400 3 103/μL, signifying thrombocytosis, is associated with an increased risk of malignancy.2,3 A study of 102 patients who had a benign pelvic mass and 139 patients whose tumor was malignant or classified as borderline determined that thrombocytosis was present in 16% of women who had a benign pelvic mass and 56% of women who had a malignant or borderline tumor.2
Preoperative thrombocytosis has also been reported in children and adolescents who have a germ cell tumor.3
The lesson? Before you operate on a pelvic mass, check the platelet count!
1. Timmerman D, Testa AC, Bourne T, et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol. 2008;31(6):681-690.
2. Chalas E, Welshinger M, Engellener W, Chumas J, Barbieri R, Mann WJ. The clinical significance of thrombocytosis in women presenting with a pelvic mass. Am J Obstet Gynecol. 1992;166(3):974-977.
3. Haddad LB, Laufer MR. Thrombocytosis associated with malignant ovarian lesions within a pediatric/adolescent population. J Pediatr Adolesc Gynecol. 2008;21(5):243-246.