PAA was first reported in 1898 and first summarized in cases in 1950 [1]. As a severe complication, in adult PA patients, the overall incidence of apoplexy is 0.6–25% [13, 17, 23, 25], and it is more likely to occur in those aged 30–50 years [32]. Hypotheses concerning the pathogenesis of PAA include the following: hypertension [13, 21] or acute hypotension [20, 26]; history of pelvic, cardiac, or vascular surgery [11, 13, 31]; history of anti-platelet and/or anticoagulant medication [11, 13, 17, 18, 26]; history of gonadotropin-releasing hormone medication [21] or dopamine-agonist medication4; trauma [21]; presence of aneurysms [22]; and radiotherapy [21, 31]. However, none of the pediatric and adolescent patients in the present study had any of the above histories or clinical features. Large tumor size [18], imbalance of high local metabolism, and low nutritional status [20] may also lead to local vascular occlusion and rupturing, and may result in the development of apoplexy. Moreover, molecular factors (e.g., vascular endothelial growth factor [12], high-mobility group box1 [19], oestrogen [14], and AIP mutation [27]) may also contribute to the development of apoplexy by altering microvascular permeability, promoting local subacute intra-tumoral inflammatory responses, and inducing faster growth of tumor cells. However, PAA has not been thoroughly described in pediatric and adolescent patients due to limited published cases.
In the present study, apoplexy was found in 42.5% of pediatric and adolescent PAs. This result is consistent with previous reports that the prevalence of PAA in pediatric and adolescent patients is higher than that in adult patients (approximately 0.6–25%) [13, 17, 23, 25]. Moreover, consistent with previous reports, although apoplexy is more frequently found in non-functional tumors in adults [33], are present study corroborated that more PAs with apoplexy are functional tumors in pediatric and adolescent patients [6, 16]. Although the precise reason for this phenomenon remains unclear, there are some plausible speculations. In adult patients, functional PAs are often detected by specific hormone-secreting symptoms, while non-functional PAs are often detected by apoplexy causing a sudden increase in tumor size and an obvious occupying effect. In contrast, the majority of PAs in pediatric and adolescent patients are functional [3, 9, 10], and non-functioning PA is extremely rare in young patients [28]. Moreover, hormonal symptoms cannot be easily identified in the growing stages of each organ; therefore, apoplexy-related symptoms are frequently found in functional PAs in younger patients.
Some authors have reported that in pediatric and adolescent patients, PAA may be associated with tumor size, tumor invasiveness, and PRL-secretory type [33]. However, others studies have not found such associations [15]. Similarly, in our present study, apoplexy did not relate to tumor size, Knosp/Hardy-Wilson classifications, or PRL tumors. Nevertheless, our results indicate that, as in adult patients [13], PAA is significantly associated with preoperative visual loss and/or deficits in pediatric and adolescent patients. Although surgery improved visual function in both groups, the postoperative VIS of the apoplexy group was still worse than that of the non-apoplexy group. In these cases, early surgery to decompress the optic nerves is critical. It has been reported that it is optimal to operate within one week or even 48 h, which can reduce the rate of disability [2, 24]. Therefore, appropriate surgical management is essential for pediatric and adolescent patients with PAA to salvage visual function. Moreover, our present findings suggest that young PA patients with apoplexy might have a higher Ki-67 proliferation index than those without apoplexy (P=0.070), indicating that apoplexy-inducing PAs may have a tendency for rapid growth; if so, this would induce an insufficient blood supply and an ischemic-hypoxic tumor microenvironment, leading to PAA [29].
We also investigated the effect of apoplexy on tumor recurrence in pediatric and adolescent patients. We found that the presence of tumor apoplexy did not affect tumor resection, and was not associated with tumor recurrence. Furthermore, using multivariate analysis, only STR was found to be independently associated with recurrence, and Knosp classification correlated with resection rate.
Limitations
Our study had the following limitations. This was a retrospective study with a limited sample size, and bias may have existed. Thus, more favorable clinical evidence is still needed from subsequent large-sample prospective studies.