Rapid recurrence of stage IIB non-gestational ovarian choriocarcinoma with minor yolk sac tumor: A rare case report and literature review

Highlights • Non-gestational ovarian choriocarcinoma (NGOC) is rare.• NGOC can behave aggressively with poor survival and high recurrence rates.• Expert pathology evaluation is warranted given its rarity.• Individualized care and close monitoring is crucial for NGOC management.• Fertility preservation for NGOC is feasible in select cases.


Introduction
With an incidence of less than 0.6 % of malignant ovarian tumors, non-gestational ovarian choriocarcinoma (NGOC) is both aggressive and extremely rare (Cronin et al., 2022).It necessitates special attention due to its close resemblance in presentation to gestational ovarian choriocarcinoma (GOC).They often present in a similar manner to ectopic pregnancies, with pelvic pain, abnormal bleeding, and elevated β-human chorionic gonadotropin (β-hCG).Tissue analysis for lack of paternal genetic components effectively makes the diagnosis of NGOC.Initial evaluation typically involves: a comprehensive gynecologic history, evaluating fertility potential, obtaining β-hCG levels, and ultrasound imaging.Once other differential diagnoses are ruled out, and NGOC is suspected, comprehensive computed tomography (CT) scans will assist in ruling out metastasis in the liver, lungs, and pelvis.Treatment often requires surgical resection and chemotherapy; most commonly utilizing Bleomycin, Etoposide, and Cisplatin (BEP) (Cronin et al., 2022).With a timely response to initial presentation, patients can be offered fertility sparing options with potential long-term survival (Cronin et al., 2022).Close monitoring and long-term surveillance following surgery and chemotherapy are important conclusive steps.
Most patients are fortunate to have positive outcomes with an ability to maintain fertility.

Case
An 18-year-old nulliparous female presented to the emergency department (ED) with constipation and abdominal pain for the past month.Upon presentation, β-hCG was > 100,000 mIU/mL.She denied ever being sexually active and reported a history of irregular menstrual cycles.Pelvic ultrasound demonstrated a 13 cm pelvic mass, with thecalutein cysts, and without an associated intrauterine pregnancy.Further investigation with CT of the chest, abdomen, and pelvis revealed multiple complex cystic masses in both adnexa measuring up to 15.5 cm and 13.6 cm as well as several small nodular peritoneal implants [Fig. 1 A, B,  C], [Fig. 2 A, B, C, D].
Fertility-preservation with exploratory laparotomy, unilateral salpingo-oophorectomy, peritoneal biopsies, total omentectomy, and pelvic and aortic lymphadenectomy was completed, revealing a stage IIB non-gestational ovarian choriocarcinoma with a minor yolk-sac tumor component and dysgerminoma.
During her recovery, barely one-month after surgery, she presented to the ED with an acute abdomen and findings of peritonitis secondary to bowel rupture from recurrent tumor invasion to the sigmoid colon [Fig.1C].At that time, she underwent an urgent laparotomy inclusive of a complete modified radical hysterectomy, abdominal washout, with en-bloc unilateral salpingo-oophorectomy, rectosigmoid resection and descending colostomy.She experienced a 9-day intensive care unit (ICU) stay during which she required vasopressors, parenteral nutrition, antimicrobials, and blood transfusions.She was ultimately discharged home on post-operative day-18 after she met all her milestones for discharge.Prior to initiation of chemotherapy, her β-hCG was down to 83 mIU/mL.She ultimately went on to complete 8-cycles of EMA-CO without radiographic findings of disease recurrence.She had repeat β-hCG levels every month that remained undetectable during the surveillance period.She eventually had her colostomy reversed and remains disease free after 21-months.

Methods
An extensive literature search for peer-reviewed articles written in the English language was performed, keywords such as non-gestational ovarian choriocarcinoma and fertility-preserving surgery were primarily used to review/search for publications through Google, PubMed, and the NIH National Library of Medicine.Further article retrieval was obtained from the references of well-cited publications, and a relevant list of cases was formed [Table 1] [see also Supplement 1 -for Extra List of References].
Cases have been excluded because of the lack of relevance to our reported case.Reasons include tumors located in the female reproductive system that were not NGOC or GOC in nature.Cases dated prior to the year 1995 were also excluded to highlight relatively modern efficacious chemotherapy methods, and the trends in accepted treatments that more closely resemble currently available options.

Discussion
NGOC is a highly aggressive neoplasm, but it is also rare.Only 57 cases have been reported in the peer-reviewed literature since the year 1995, with ever-increasing achievements in maintaining fertility.Chemotherapy with BEP is the most utilized standard of care after fertility preserving surgery and is associated with a high response rate (Cronin et al., 2022).Fertility-sparing surgery for early-stage disease is a reasonable first option, given that the peak incidence of NGOC occurs during early reproductive years (Adow et al., 2021).More radical surgical approaches are required in advanced stages in combination with well-studied adjunct chemotherapy regimens.

Outcomes
Of the 58 known cases (including our own), 38 (66.6 %) cases were known to be disease-free following surgery and/or chemotherapy, 10 (17.5 %) cases died, and nine (15.8 %) cases were lost to follow-up [Table1] [see also Supplement 1 -for Extra List of References].Surveillance: The β-hCG levels are a relatively poor prognostic indicator.Our literature review provided a limited number of cases that reported these numbers.The average β-hCG levels among deceased patients was 175,868 mIU/mL (n = 6) and among the disease-free patients, it was 265,952 mIU/mL (n = 32).An extremely limiting factor regarding β-hCG is the timing at which the levels were acquired.Some cases tracked levels after chemotherapy had begun, and others did not track them at all.Follow-up levels of zero are more helpful with a prior elevated β-hCG level to compare with.

Treatment
An emphasis on fertility-sparing treatment options was imperative for this patient population.53 out of the 58 cases (91.3 %) were younger than 51; the average age of menopause.It is unclear how many of these patients endorsed a desire to maintain fertility, or how many children each respective patient already had.In any case, this is a portion of the risks that ought to be discussed early on in a setting of shared decisionmaking.Of the 38 surgical cases, 16 (42.1 %) necessitated total abdominal hysterectomy with bilateral salpingo-oophorectomy.The remaining 22 cases (57.9 %) were able to maintain some form of fertility.Of the 37 cases in which the specific chemotherapy treatment was reported, including our case, 17 (45.9%) used BEP alone, five (13.5 %) used EMA-CO alone, and 15 (40.5 %) used another combination modality.

Prognostic factors
Of the 39 cases known to be disease free, 32 (82.1 %) utilized both surgery and chemotherapy.Of the 10 cases known to have died, six (60 %) also utilized both methods.There is not enough evidence to draw conclusions based on these numbers, but the dual approach to treating NGOC is the most commonly demonstrated.Fourteen (82.4 %) patients treated with BEP alone survived with two deaths and one unknown outcome.Four patients treated with EMA-CO alone survived (80 %), with one unknown outcome.Eleven patients treated with another combination modality survived (73.3 %), with four deaths.More details can be found in

Conclusion
NGOC is an exceptionally rare and aggressive ovarian malignancy, necessitating a careful balance between appropriate treatment and maintenance of fertility.It is difficult to distinguish, and a delay in diagnosis can increase the possibility of necessitating more aggressive surgical resection.The majority of patients affected by NGOC will likely be women of child-bearing age; therefore, their outcomes in prognosis and fertility are best when assessed early on and a shared treatment plan can begin as soon as possible.

Precis
Primary and recurrent non-gestational ovarian choriocarcinomas are rare with generally poor prognosis; however, opportunities exist to optimize cancer control.

Consent
Informed consent was obtained from the patient for publication of this case report and accompanying images.

Fig. 1 .
Fig. 1. (A) Computed tomography (CT) anterior/posterior (A/P) coronal and transverse.Multiple complex cystic masses in both adnexa measuring up to 15.5 cm and 13.6 cm.(B) CT A/P coronal and sagittal.Multiple complex cystic masses in both adnexa.(C) CT A/P coronal and sagittal.Peritonitis secondary to bowel rupture from tumor invasion to the sigmoid colon.

Table 1
[see also Supplement 1 -for Extra List of References].

Table 1
Treatment and outcomes of known cases of NGOC from the year 1995 to present.[see also Supplement 1 -for Extra List of References].