Mucinous cystadenocarcinoma of the ovary in a 14-year-old girl: a case report and literature review

Here we reported a case of ovarian mucinous adenocarcinoma in a 14-year-old girl, which to our knowledge is the first case of ovarian epithelial tumor reported so far in Chinese and East Asian children. Of the eight cases of mucinous adenocarcinoma that have been previously reported in the literature worldwide, seven were from Europe or the United States, and one was from India. Some studies have suggested that ovarian cancer incidence may be related to race and ethnicity, with rates among white adolescents and young adults almost twice as high as those among black women of the same age group [12]. The question of whether racial and ethnic differences are also associated with the incidence of ovarian epithelial tumors in children has been so far unanswered, partly because of the few reported cases. Thus, continued attention and further research are needed in this regard.

In previous reports on mucinous carcinoma of the ovary in children under 15 years of age, the clinical and pathological features of the patients showed that most of the patients had abdominal pain and distention as their first symptoms; elevated serum tumor marker CA125 was reported in two cases, and mildly elevated HCG was reported in one case. None of these reports had follow-up of the patients’ postoperative menstrual status. In the present case, the patient did not have abdominal pain and distension, but presented with a small amount of bloody vaginal discharge. Through follow-up interviews, we know that her current menstrual cycle is about 15 days, with an average period of 3–4 days, low volume, and no dysmenorrhea.

Epithelial tumors of the ovary are very common in women, and most commonly occur during adulthood. Of note, the types of ovarian tumors occurring in children before the age of 15 differ from those diagnosed in adults, with a majority of sex cord-stromal and germ cell tumors, and less than 20% of epithelial tumors. In this line, Van et al. [13] reported ovarian masses in infancy, childhood and adolescence, with the incidence of epithelial and germ cell tumors being 15% and 70%, respectively in the under-15 age group, and 41% and 43% in the over-15 age group. Similar findings were obtained by Young et al. [12] and Li et al. [14].

Concerning ovarian cancer pathogenesis, the traditional view is that all ovarian cancer subtypes originate at the surface epithelium of the ovary. During ovulation, damage to the ovarian surface is caused by the follicle rupture and consequent oocyte release, and during damage repair, the epithelial cells on the ovarian surface become invaginated and form cortical cysts. Exposure of epithelial cells lining the cortical cyst to a new hormone-rich environment induces their proliferation, and eventually some epithelial cells that happen to harbor remaining DNA damage may become carcinogenic, thus leading to ovarian cancer [15]. This rationale explains those ovarian epithelial malignant tumors occurring after menarche but not the cases that occur before it. Consistently, the characteristics of ovarian epithelial tumors are different between children and adults, with serous tumors being the most common in adults while mucinous tumors are the most common in children. It has been suggested that some of the mucinous tumors in the age group of 10–14 may originate from monoblastic differentiation of the gastrointestinal mucinous epithelium in teratomas [16]. This is the age at which germ cell tumors are prone to occur, which may explain why a proportion of mucinous tumors occur before menarche.

The main mode of presentation of ovarian epithelial tumors was abdominal pain, bloating or menstrual disturbances with vague symptoms that were initially ignored. The girl reported in this case presented with a small amount of bloody vaginal discharge, which opportunely caught her attention. Notably, approximately 21% of patients with ovarian epithelial tumors are asymptomatic [14], which frequently leads to disease progression before the lesion is diagnosed.

Both analysis of tumor markers as well as radiological studies are important tools in the diagnosis of ovarian cancer [17]. CA 125 has been widely used as a marker for epithelial ovarian tumors, however, its positive predictive value is debatable. Although serum CA 125 levels (> 35 U/mL) are elevated in more than 80% of patients with ovarian epithelial carcinoma, they are also elevated in approximately 1% of non-neoplastic conditions such as endometriosis, cirrhosis, pancreatitis, pelvic inflammatory disease, and advanced abdominal -non-ovarian- malignancies [18]. Furthermore, serum CA 125 has been reported to have only 78.1% sensitivity and 76.8% specificity in detecting primary ovarian epithelial carcinoma [19]. In spite of this, it remains a useful tumor marker to be used in combination with imaging findings, which often show an adnexal mass in the presence of a tumor.

Frailty, characterized by increased vulnerability and reduced health response, plays an important role in predicting postoperative complications and survival outcomes in gynecological oncology. This assessment, which correlates with prolonged hospital stay and increased risk of organ failure, mortality, and rehospitalization, should be performed using standard scores such as the Clinical Frailty Scale (CFS-7) and Frailty Index (FI), [20]. This enables personalized therapeutic strategies for patients with gynecological malignancies, thereby improving oncological outcomes. Although we assessed her body mass index (BMI), nutritional status, general vital signs, psychosocial status, and risk factors for stress-related injury and concluded that she was likely to tolerate surgery with minimal risk of serious complications, we did not use specific frailty measures (e.g., CFS-7, FI) We recognize the importance of these assessments and acknowledge this as an area for future improvement.

Following surgery, the patient developed a low-grade fever, and complete blood count (CBC) indicated an elevated white blood cell count and neutrophil percentage, warranting antibiotic treatment. Postoperative pain was managed with pain management therapy, resulting in only mild discomfort, as indicated by a Visual Analogue Scale (VAS) score of less than 3. No other postoperative complications were observed.

The prognosis of ovarian cancers presenting at a young age is variable and depends on the tumor stage upon presentation as well as histological type. In the eight reported cases of ovarian mucinous carcinoma in children to date, five were at stage I. Among these, one case was found to have cancerous thrombi in the vessels and died from recurrent metastasis two years later, while the rest achieved a survival time of over five years. The other three cases were at a higher stage: one died a year after diagnosis, and the other two had either metastasis at the time of diagnosis or cancer cells were found in the ascites, suggesting a less favorable prognosis.

Treatment of ovarian epithelial carcinoma in children relies on the experience from treating adult patients, with an emphasis on the preservation of reproductive functions. However, individualized regimens have been developed based on the establishment of comprehensive surgical staging. In patients with low-grade stage IA (serous, endometrioid or mucinous expansile subtype), fertility-sparing surgery (FSS) appears to be a safe option [21,22,23]. FSS can also be considered for stage IC1 tumors, as recurrences, which are often isolated on the remaining ovary, can typically be managed with subsequent surgery. However, it’s important to note that recurrence rates tend to be higher in stage IC2, IC3, and grade 3 diseases, mainly in extra-ovarian sites. This suggests that these recurrences may not be directly associated with the fertility-sparing approach. Therefore, comprehensive counseling is crucial when considering FSS in these situations [24].

Various adjuvant chemotherapy regimens have been used in epithelial carcinoma of the ovary to improve survival. A comprehensive cohort study [25] found that chemotherapy not only reduced mortality for high-risk patients but also for those with stage IA/IB, grade 2 ovarian cancer. This aligns with previous studies showing no advantage of chemotherapy for women with stage IA and IB, grade 1 tumors. In particular, for histological subtypes like mucinous subtype, the expansile or grade I type, which is linked to a better prognosis, is not recommended for adjuvant chemotherapy, while the infiltrative form has a high relapse risk [26,27,28,29].