Unique features of pregnancy-related meningiomas: lessons learned from 148 reported cases and theoretical implications of a prolactin modulated pathogenesis

Abstract

Meningiomas are some of the most frequently encountered adult intracranial tumors. Dramatic flare ups in size may occasionally be observed during pregnancy, leading to complicated clinical scenarios, with profound effects and substantial risks for both the mother's and the fetus's well-being. Despite the fact that such changes have largely been attributed to progesterone-based mechanisms, recent studies have put this theory into question or defied it. In order to assess these particular tumors carefully and to try and clarify the pathophysiology of such pregnancy-related meningioma growth, an in-depth review of the pertinent literature was undertaken. Based on clinical, radiographic, and pathological data gathered from 148 reported cases, we have found several unique features characterizing these pregnancy-related meningiomas. The presence of such observed features was found to be of high statistical significance when compared to their expected prevalence in the general population and included the following: (1) parasellar location, (2) anterior circulation blood supply, (3) visual symptoms at presentation, (4) high rate of clear-cell and chordoid morphology. A hypothesis is developed that these features are related to hormonal influences of the pituitary gland, and we discuss that this may be due to elevated prolactin levels. We encourage further research to test this exciting new theory.

Pathologic Characteristics of Pregnancy-Related Meningiomas

“…Pregnancy-related accelerated growth is mainly observed during the second and third trimesters, which coincides temporally with increasing prolactin levels, thus supporting this notion [24][25][26]. Pregnancy-related meningiomas were more often of chordoid (6%) or clear-cell types (4%) [23], as compared to meningiomas in the background population, which were 0.5% [27] and 0.2% [28], respectively. Combined with the findings that 40-60% of meningiomas are prolactin receptor-positive [23], the authors raise the hypothesis that meningioma growth during pregnancy may be affected by prolactin.…”

“…A labeling index over 4% was associated with an increased recurrence rate [39]. In the aforementioned review in pregnancy-related meningiomas, a mean Ki-67 labeling index of 6.63% was found [23].…”

“…Pregnancy-related meningiomas were more often of chordoid (6%) or clear-cell types (4%) [23], as compared to meningiomas in the background population, which were 0.5% [27] and 0.2% [28], respectively. Combined with the findings that 40-60% of meningiomas are prolactin receptor-positive [23], the authors raise the hypothesis that meningioma growth during pregnancy may be affected by prolactin.…”

“…The well-known phenomenon of explosive growth of an already known meningioma that occurs in some women during pregnancy remains puzzling [20][21][22]. A review points out that pregnancy-related meningiomas are more likely to be located near the pituitary gland than other meningiomas [23]. The authors speculate that meningiomas supplied by the anterior circulation may be exposed to prolactin.…”

“…The arguments underlying the hypothesis are (1) prolactin is secreted by the anterior pituitary gland [29], (2) the plasma concentration of prolactin during pregnancy reaches its peak at term [30], (3) prolactin accelerates the proliferation rate of meningioma-derived cells in vitro [31][32][33], (4) prolactin is both a circulating hormone and paracrine/autocrine factor participating in angiogenesis [34], which is important in the tumorigenesis process of, for example, meningiomas [35], and (5) prolactin has a pivotal role in osmoregulation in various cells and tissues [36,37]. It is speculated that this last feature could be responsible for the rapid changes in meningioma volume, which can be observed during and after pregnancy [23]. In summary, there are currently three underlying prolactin-related theories of drastic meningioma volume changes observed during and after pregnancy: angiogenesis, osmotic regulation and proliferative activity.…”