Epithelial
Serous
15–20%
Mucinous
Endometrioid
Clear cell
Transitional cell
Epithelial-stromal (adenosarcoma, carcinosarcoma)
Nonepithelial
Germ cell
Dysgerminoma
60–80%
Yolk sac
Monodermal
Mixed
Teratoma
Sex cord stromal
Granulosa cell
10–20%
Sertoli-Leydig
Mixed
Metastases
The malignancy risk has been evaluated in an epidemiologic study including more than 1000 cases [6] in which the risk stratification has clearly showed that, related to the frequency of onset of ovarian masses, the malignancy rate is proportionally higher in the 1–8 years group; in this age group, in fact, it is extremely rare the presence of an ovarian neoformation of functional nature and therefore the risk to be in the presence of a neoplasia is significantly higher. This is why in this age group the clinical approach, in case of ovarian mass, has to be more prudent.
Other studies have put in evidence that, besides patient’s age, other characteristics are related to malignancy risk: clinical and hormonal features of precocious puberty or virilization (abnormal hormonal function), dimensions >8–10 cm, presence of solid components inside the formation, higher level of one or more tumor markers. However, in the pediatric age it doesn’t exist yet a reliable and validated tool able to distinguish, like in the adult population, a benign from a malignant ovarian mass. In fact, while a number of such tools (risk indexes, diagnostic algorithms) have been developed for the reproductive and menopausal age (RMI, ROMA; OVA1, LR2 and, recently, a new algorithm involving the use of protein HE4), in the pediatric age similar efforts have not allowed similar results, perhaps due to the eterogeneicity of the studied populations and to the small number of ovarian malignancies: with these premises, so that whatever complex diagnostic tool requires very difficult and time-consuming validation.
Box 1: Differential Diagnoses of Ovarian Cysts
Hydrosalpynx
Paraovarian cyst
Hematometra/hematocolpos
Salpyngitis
Pelvic abscess
Extrauterine pregnancy
Abdominopelvic cysts not ovarian
11.3 Diagnosis
Symptoms associated with the presence of an ovarian mass are extremely variable, coming from the total lack of any symptom (it is frequent their occasional detection during imaging studies for other reason) to pelvic/abdominal pain (chronic/recurrent or acute), until clinical signs of abnormal hormonal secretion (precocious puberty, virilization, dysfunctional uterine bleedings, etc.). There have also been reported rare clinical manifestations associated to the presence of mature teratomas, very similar to paraneoplastic syndromes, such as autoimmune hemolytic anemia and immune-mediated limbic encephalitis [7, 8].
Generally, complex masses and in particular mature cystic teratomas can become symptomatic because of their related complications: torsion (3–16%), rupture (1–4%), infection (1%), malignant degeneration (0.17–2%).
Since presenting signs and symptoms of ovarian masses (either benign or malignant) are so heterogeneous, in recent years many authors have looked for clinical and/or imaging features in order to exclude the risk of malignancy and to increase the number of patients candidates to ovarian preservation (wait-and-see policy, re-evaluation, laparoscopic surgery, reduced number of oophorectomy).
Ultrasonography: In the diagnostic approach, it remains the primary tool either for the precocious diagnosis or the follow-up, offering the possibility to reassess in a reasonable time masses potentially suspicious so avoiding aggressive treatments. Ultrasonography has, in fact, the basic requirements of spread, ease of use, and to repeat. Ultrasonographically, the mass is considered for its main features that are dimensions, appearance, and content, which should help in choosing the best therapeutic approach. When the cyst is unilocular, unilateral, with thin and smooth wall, smaller than 8 cm and without ascitic fluid, the risk of malignancy is very low (<1%).
US is the initial modality to confirm the presence of adnexal masses and provides their approximate size. In some cases, it characterizes the mass, such as a dermoid cyst, by showing calcification and fat-fluid level.
Malignancies are more often complex masses with irregular edges, not well defined, often with necrotic central areas, sepiments, and papillary projections. When ultrasonography, even repeated after 6–8 weeks, is not diriment, the second diagnostic step is represented by Magnetic Resonance Imaging; the use of Computed Tomography is only reserved for the staging of histologically proven malignancies.
Traditionally, masses greater than 5 cm have been used as cutoff suggestive of malignancy, with some studies using 7.5 and 8 cm. A recent study by Papic et al. [9] showed that 56% of benign masses were >8 cm so the cutoff value of >10 cm has been proposed as a malignancy predictor, as well as the presence of solid components seen on imaging. Neither of these predictors was independently 100% sensitive for malignancy, as 11% of malignant masses were <10 cm and 22% of malignant masses were cystic (complex) with no solid components.
Magnetic resonance imaging: Preoperative pelvic MRI findings might change the surgical management of pediatric patients with adnexal masses, so it is considered a valuable addition to the conventional workup in the clinical management, especially when an extraovarian origin of the mass is suspected or a malignancy has to be ruled out. In a study of Marro et al. [10], MRI correctly suggested benign nature in 24 of 28 (85.7%) benign masses while US was indeterminate in 19 of these 28 (67.8%) masses. MRI is required for better characterization of ovarian masses, for assessing likelihood of malignancy, and for staging the tumor. It is chosen for staging of malignancy over CT scan to reduce ionizing radiation exposure in this young and more vulnerable population.
Tumor markers: Their diagnostic significance is controversial for the possibility of higher plasmatic values either in malignant or in benign masses: in the Literature the rate of benign lesions associated with markers elevated values varies from 3.4 to 20%, while no more than half of the malignant forms have a higher value of one or more markers. It creates the risk to underestimate the possibility of malignancy, but even that of planning a too aggressive approach toward a benign lesion.
A recent paper dealing with pediatric age [9] has evidentiated that alpha-fetoprotein and beta-HCG are highly specific for neoplastic masses since in the analyzed series no benign mass was associated with elevated values of these markers. But the same study has identified 17% of patients with malignancies showing the absence of any marker elevation, coming to the conclusion that the absence of tumor markers modifications does not allow to exclude the presence of malignancy.
On the basis of such considerations, it appears reasonable to always program an extemporaneous histologic examination when tumor markers are elevated, in order to offer the most appropriate surgical approach, but never to plan an aggressive surgical approach only relying on tumor markers.
However, their use is always considered useful during follow-up of malignancies, either to evaluate the answer to therapy or to early detect recurrences.
Hormones: Hormonal samples are mandatory when an abnormal hormonal production is suspected (precocious puberty, virilization, hyperthyroidism, etc.). Inhibin-B, progesterone, and Anti-Mullerian Hormone (AMH) are other hormones actually under validation as possible pre- and postoperative “markers” of reduced ovarian reserve, coming from the mass itself and/or from its surgical treatment (open surgery or laparoscopy).
11.4 Therapy
About 60% of ovarian masses are treated surgically. Nowadays, more than 50% of surgeries for ovarian masses in adolescents are performed laparoscopically, and most of the patients (71–84%) undergo cystectomy rather than oophorectomy. However, of the small number of patients who undergo oophorectomy, the majority have benign lesions, and this has to be considered unacceptable, although still performed.
The best practical treatment of pediatric and adolescent ovarian masses is not a well-defined topic because of the lack of markers or validated indicators of malignancy. Considering neoplastic masses, very different approaches are described and followed, particularly for stadiation of germ cell tumors compared to epithelial and stromal, having developed in recent years extremely conservative strategies for the first ones (such as laparoscopy, ovary-sparing surgery, tumorectomy with preservation of residual ovarian tissue) and more aggressive for the others. In recent years, preservation rates in girls with benign ovarian masses have increased from 15% in 1999 to 39–61%, but as stated by Papic et al. [9] it is likely less than it could be.
Besides, it is always dutiful to consider that for many ovarian neoplasms the surgical treatment is needed as an emergency procedure because of a secondary torsion or rupture.
The main target in the management of an ovarian mass in pediatric and adolescent age should be to preserve the ovary, without betraying the oncological principles, most of all as far as it regards the stadiation, considering that during surgery the histology is not known until pathologic exam is performed.
The general basic rules in the management of ovarian masses in this age group should therefore be the following:
- 1.
To establish cyst/mass main features
- 2.
To avoid any surgery for functional cysts
- 3.
To exclude the presence of neoplasms
Laparoscopic surgery is considered the gold standard in the treatment of benign ovarian masses. There are still existing controversies regarding malignancies, and for this reason a lot of “suspected” masses are still treated with laparotomies by gynecologists and pediatric surgeons. While there is general agreement about the use of laparoscopy when a malignancy is reasonably excluded during preoperative evaluation, there are not precise rules to achieve this “reasonably exclusion,” although some authors have published data aimed to this.
There are two main stadiation systems for ovarian pediatric masses: one from the International Federation of Gynecology and Obstetrics (FIGO) and one from the Children’s Oncology Group (COG), regarding only germ cell tumors (Tables 11.2 and 11.3). The Children’s Oncology Group (COG) established also the current consensus guidelines for appropriate staging procedures among pediatric patients with ovarian germ cell tumors [11] (Table 11.4).
Table 11.2
2014 FIGO ovarian cancer staging
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