Are Ovarian Inclusion Cysts a Precursor for Ovarian Cancer in Menopausal Women?

Abstract & Commentary

By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.

Dr. Coleman reports no financial relationship relevant to this field of study.

Synopsis: One hypothesized etiology for the development of ovarian cancer is malignant transformation of inclusion cysts. However, their identification in menopausal women undergoing routine screening by ultrasound was not associated with an increased risk of ovarian cancer or other "estrogen-dependent"

Source: Sharma A, et al. Assessing the malignant potential of ovarian inclusion cysts in postmenopausal women within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A prospective cohort study. BJOG 2011.

The primary objective of this prospective cohort study was to evaluate the malignant potential of ultrasound-detected ovarian inclusion cysts in the development of ovarian cancer in menopausal women participating in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study. In this prospective, randomized study, women were allocated 2:1:1 to no formal screening, screening by the Risk of Ovarian Cancer algorithm, or an annual transvaginal ultrasound. This latter cohort, consisting of 48,230 women aged 55-74, formed the investigative sample for this publication. Women with ovarian inclusion cysts defined as single or multiple anechoic cysts, 10 mm or less in size, and normal ovaries (both uniform hypoechogenicity) on their first scan were identified and tracked via cancer registry/questionnaires. The relative risk (RR) of developing ovarian cancer, breast cancer, and endometrial cancer in women with inclusion cysts was assessed relative to those with normal ovaries and the incidence rate was compared with UK age-adjusted expected rates. Overall, in the initial scan, 1234 (2.5%) women were found with inclusion cysts; 22,914 had normal scans. After a median follow-up of 6.13 years, three of 1234 women with inclusion cysts were diagnosed with invasive ovarian cancer, compared to 29 of 22,914 women with normal ovaries (RR 1.92; 95% confidence interval, 0.62-5.92). Similar non-significant RR values were observed for uterine and breast cancer. In addition, there was no difference between the observed vs expected incidence rates for these cancers in women with inclusion cysts based on population controls. The authors conclude that postmenopausal women with ultrasound-detected inclusion cysts do not appear to be at increased risk of ovarian or breast/endometrial (hormone-dependent) cancers.

Commentary

There have been several theories as to the etiology of ovarian cancer, but one of the most pervasive is the malignant transformation of the ovarian surface epithelia trapped in the ovarian stroma via injury/healing of the cortex.1 Epidemiological studies have connected lifetime ovulatory events ("incessant ovulation") with increased risk of ovarian cancer and, conversely, lower risk among women taking hormonal contraception or experiencing multiparity. In addition, several histology-based studies of women with ovarian cancer have demonstrated increased numbers of inclusion cysts in the contralateral unaffected ovary. Further, embryologic development of the ovarian surface epithelium and müllerian ducts are regulated by HOX genes, which, while being spatially restricted following organ formation, are responsive to sex steroids during the menstrual cycle.2 It is postulated that aberrant expression of these genes in inclusion cysts could drive malignant proliferation and derive the variant histologies seen in ovarian cancer. However, it recently has been postulated that an alternative etiologic mechanism may derive from malignant transformation of highly specialized (secretory cells) in the fallopian tube.3 The current paper would lend credence to this alternative theory as the risk for ovarian cancer was no higher in women found with inclusion cysts than their normal counterparts, nor was there an increase relative to the age-matched control population.

This is the first prospective study to evaluate the natural history of inclusion cysts identified by ultrasound. Fortunately, they are uncommon (2.5%), often resolve (40%), and have no apparent cancer association in this context. Although the follow-up period was relatively short, few inclusion cysts persisted or became problematic. These observations are consistent with other studies of unilocular cysts (up to 10 cm) in menopausal women and their apparent lack of malignant potential.4 However, long-term studies are necessary to confirm the findings.

References

  1. Hennessy BT, et al. Ovarian cancer. Lancet 2009;374:1371-1382.
  2. Bowen NJ, et al. Emerging roles for PAX8 in ovarian cancer and endosalpingeal development. Gynecol Oncol 2007;104:331-337.
  3. Crum CP, et al. The distal fallopian tube: A new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol 2007;19:3-9.
  4. Modesitt SC, et al. Risk of malignancy in unilocular ovarian cystic tumors less than 10 centimeters in diameter. Obstet Gynecol 2003;102:594-599.