Diagnostic and therapeutic challenges of a rare large ovarian strumal carcinoid in pregnancy, about a case report

Abstract

Introduction

Ovarian strumal carcinoid is a rare type of germ cell tumor. It usually affects perimenopausal and postmenopausal women. Very few cases of stromal carcinoid have been reported in the literature in women of childbearing age, particularly during pregnancy. The clinical presentation of the tumor, and in particular its non-specific clinical and radiological appearance and rarity, explain the difficulties in diagnosis and management.

Presentation of case

Herein, we describe a rare case of a 36-year-old patient who was followed-up in our outpatient clinic for organic cyst of the ovary. The ultrasound revealed a multilocular regular cystic mass with a modestly thickened wall and fine septations. The MRI indicated a right ovarian cyst with solid tissue. The levels of tumor markers were normal. The patient was lost to follow-up and did not return until six months later. She was admitted in our Department with acute ovarian torsion and underwent emergency surgery at 17 weeks' gestation. A laparoscopic cystectomy of the right ovary was provisionally performed. Pathology revealed an ovarian strumal carcinoid tumor.

Discussion

Patients with ovarian stromal carcinoid have an excellent prognosis. Ovarian strumal carcinoid ‘s primary therapy method is operation. The majority of original ovarian carcinoid tumors progress slowly, and practically all thyroid carcinoid tumors are clinical stage I with a positive prognosis.

Conclusion

In the absence of standardized treatment, the association of carcinoid strumal tumor with pregnancy, underlines the need for early diagnosis and appropriate multidisciplinary management, taking into account both the maternal and fetal prognosis.

Highlights

• •Strumal carcinoid tumor of the ovary is a rare and unique teratoma of the ovary, which consists of thyroid tissue mixed with neuroendocrine neoplasm.
• •These tumors frequently have no symptoms or are accompanied by vague signs like the diffuse abdomen ache in this instance.
• •The presence of ovarian stromal tumor cannot be predicted preoperatively based solely on clinical symptoms, ultrasound data, radiographic and macroscopic examination makes distinguishing ovarian stromal tumor from ovarian cancer challenging.
• •Patients with ovarian stromal carcinoid have an excellent prognosis.

1. Introduction

Ovarian stromal carcinoid is a rare monodermal germ cell tumor composed of thyroid tissue and carcinoid components. This tumor accounts for less than 1 % of all ovarian cancers and 3 % of mature teratomas [1]. It is often unilateral and occurs most commonly in perimenopausal and postmenopausal women [2]. It is rarely seen in pregnant women [3].

This particular ovarian teratoma poses problems for preoperative diagnosis due to the non-specificity of its symmetries and its various manifestations on imaging [2], which complicates its identification and treatment protocols. Consequently, the importance of this case report becomes clear, highlighting an uncommon manifestation and the complexities involved in the management of such ovarian tumors, particularly in pregnant women.

2. Case presentation

We report the case of a 36-year-old nulliparous patient who had complained of bloating for 6 months. She had abdominal distension and mild widespread paroxysmal pelvic pain. Her menstrual cycles were regular, and she had no unusual uterine bleeding. She had no family history of ovarian or breast cancer and no personal medical or surgical history. On gynecological examination revealed a large palpable mass in the right iliac fossa and right flank with poor mobility, clear demarcation, a smooth surface, and slight tenderness.

2.1. Diagnostic

Ultrasound showed a 158 × 114 mm multilocular regular cystic mass with a slightly thickened wall and fine septations on the right ovary. Low velocity and low resistance blood flow signals were noted around the mass. There was no fluid in the Douglas. The uterus had a thin endometrial lining with no other significant features. No abnormalities were seen in the left ovary. The mass was graded as Ovarian-Adnexal Reporting and Data System-Ultrasound (ORADS-US) 4 with a 10 % risk of malignancy (Fig. 1).

Fig. 1.

Ultrasound picture: a 158  ×  114 mm multilocular regular cystic mass with a discreetly thickened wall (yellow arrow) and fine septations on the right ovary (blue arrow). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Additional radiological evaluation by pelvic MRI was requested to better characterise the mass. The MRI showed an ovarian cyst of the right ovary measuring 160 ∗ 105 cm with solid tissue (arrow) (Fig. 2).

Fig. 2.

Axial T1-weighted post contrast MRI image: solid component enhancement within a cystic lesion (white arrow).

Serum tumor markers (carcinoembryonic antigen (CA125), alpha-fetoprotein (AFP), and lactate dehydrogenase) were within normal limits. The human epididymal protein 4 (HE4 test) was not performed due to financial constraints. In view of these findings, the diagnosis of an organic ovarian cyst was maintained, and laparoscopic cystectomy was indicated. The patient was lost to follow-up and did not return until six months later. She was 17 weeks pregnant and presented to our emergency department with symptoms consistent with ovarian torsion.

2.2. Therapeutic interventions

After a thorough explanation of the case and the risks at 17 weeks amenorrhoea, she underwent emergency surgery. An exploratory laparoscopy was performed. During the procedure, a well-defined cystic tumor was seen arising from the right ovary. The tumor measured 16 cm by 10 cm. It had lobulated margins with a smooth exterior (Fig. 3). The left ovary, uterus, and fallopian tubes were in good condition. There was no ascites or pelvic lymphadenopathy. A peritoneal lavage was performed for cytological examination. Given the patient's age and intraoperative findings, a laparoscopic cystectomy of the right ovary was performed cautiously. The procedure was complicated by an inadvertent rupture of the cyst. Mucoid fluid was released. Given that the uterus was gravid and we had difficulty ensuring haemostasis after starting the cystectomy, we decided to perform an extraperitoneal cystectomy to minimise the risk of manipulating the uterus. The right ovary was uniformly enlarged with an uneven surface, and the tumor was indistinguishable from normal ovarian tissue. The operation went off without a hitch and the after-effects were straightforward. Histological analysis revealed a tumor growth with vague nodular architecture within a fibrous stroma that was abundant. These nodules were composed of vesicular structures of varying diameters lined by a layer of cuboidal cells with abundant blue cytoplasm and regular, rounded nuclei. There was a second tumor component with tubular and trabecular features existed. The cells were cubocylindrical in shape with elongated nuclei. Mitotic figures were quite rare. Immunohistochemistry showed that the cells of the first component expressed TTF1, but the cells of the second component expressed neuroendocrine markers such as CD56, synaptophysins and, more intensely, chromogranin A (Fig. 4). A multidisciplinary team of gynaecologists, neonatologists, and chemotherapists concluded that pelvic MRI was necessary to detect tumor implants, followed by adnexectomy at term to preserve the patient's life and reproductive outcome. The work was reported according to the SCARE criteria [4].

Fig. 3.

Macroscopic appearance of the surgical specimen: a 13 ∗ 10 cm cystic formation with smooth surface and thick cystic wall with indurated areas.

Fig. 4.

Histological section: A: Struma ovarii component (HE staining ∗ 100); B: focal mucinous component (HE ∗ 100); C: Positive chromogranin in carcinoid component (anti chromogranin antibody immunostaining ∗ 100); D: carcinoid component showing trabecular pattern (HE ∗ 100).

3. Discussion

Gynecological consultations are frequently requested for symptomatic ovarian masses [5]. Strumal carcinoid tumor of the ovary is a rare and unique teratoma of the ovary, which consists of thyroid tissue mixed with neuroendocrine neoplasm [6]. It has a very rare occurrence with 0.3–1 % incidence of all ovarian tumors and 3 % of mature teratomas [1]. Li and al in a retrospective study of 119 patients published in 2022 reported that perimenopausal and postmenopausal women are typically affected. The mean age was 49.1 years, with a median of 49.0 years (range 20–78 years) [2]. Turla and al in a systematic literature review published in 2022 reported that 53 % of the patients were postmenopausal [6]. There have only been a very small number of reports of ovarian strumal carcinoid in expectant women, which explains the difficulties in diagnosis and treatment. Because ovarian strumal carcinoid is uncommon, it is difficult to pinpoint particular risk factors. Yoo and al. examined 25 struma ovarii patients over a 13-year period in order to assess the tumor's clinical characteristics. These tumors frequently have no symptoms or are accompanied by vague signs like the diffuse abdomen ache in this instance. However, they can occasionally display symptoms of serotonin-induced carcinoid syndrome, such as facial flushing, diarrhea, wheezing, bronchospasm, carcinoid heart disease, abdominal cramps, and edema. Hormone peptide YY might result in severe constipation and excruciating feces [7]. Clinical testing for serum peptide YY is possible, but our institution does not offer this procedure. In addition, hirsutism and sexual pilosity are reported as clinical manifestations of hyperandrogenism. Endocrine disruption can manifest in some patients as episodes of hypertension, hyperglycemia, hypoglycemia, or thyroid malfunction [6]. No endocrine dysfunctional symptoms were present in our case.

There is no typical appearance on ultrasound. The tumors are often large and manifested as unilateral cystic or solid-cystic mixed echo [8]. International Ovarian Tumor Analysis (IOTA) or the O-RADS can be applied to evaluate the risk of malignancy [9]. It is not well known how tumor markers like CA125 and carcinoembryonic antigen are used to diagnose ovarian stromal carcinoid here are rare reported cases describing patients with ovarian strumal carcinoid who had elevated levels of both carcinoembryonic antigen (CEA) and CA125. More cases and longer follow-up periods are required to assess whether HE4 can increase the accuracy of ovarian teratoma diagnoses, according to a case study that suggested a correlation between the level of HE4 and the diagnosis of struma ovarii [10]. MRI can show a large multilobulated cystic mass with irregularly thickened septa and solid components originating in ovarian sclerosing stromal tumors [11].

The presence of an ovarian stromal tumor cannot be predicted preoperatively on the basis of clinical symptoms, ultrasound data, radiographic and macroscopic examination alone, making it difficult to differentiate ovarian stromal tumors from ovarian cancer [12]. Furthermore, ovarian stromal tumors might appear very vascular at times, complicating the differential diagnosis. Although computed tomography and magnetic resonance imaging may be helpful in the diagnosis of ovarian stromal tumor [13], pathological features continue to be the most essential factors in the diagnosis of ovarian stromal tumor. Patients with ovarian stromal carcinoid have an excellent prognosis. Kong and al in a cohort study of 56 patients published in 2023 reported that the prognosis was excellent, and conservative surgery was an effective treatment option [14]. Ovarian strumal carcinoid ‘s primary therapy method is operation. The majority of original ovarian carcinoid tumors progress slowly, and practically all thyroid carcinoid tumors are clinical stage I with a positive prognosis. Different therapy regimens should be followed depending on the patient's age, stage, and reproductive needs. If the tumor is restricted to the ovary in individuals in clinical stage I, the young patient with fertility requirements may have unilateral salpingo-oophorectomy. For older patients who have lost reproductive function, complete hysterectomy, bilateral salpingo-oophorectomy, or cytoreductive surgery are options. Patients with rare ovarian carcinoid mucin variations may additionally require omentectomy and para-aortic lymphadenectomy, as these tumors spread largely through lymphatic channels [14]. Despite the fact that laparoscopy is a risky procedure, it was chosen. Several studies have been undertaken to identify predictors of pain development following laparoscopic adnexectomy, but no consensus has been reached. Some studies claim that minimally invasive surgery is worse than open surgery, however others have identified other factors such as age, BMI, and preoperative discomfort [15].

The morphological examination of stromal carcinoid showed struma ovarii with a thyroid follicle-like structure, positive for thyroid transcription factor 1, thyroglobulin, CD56, cytokeratin, and a neuroendocrine cell component with a trabecular arrangement and island growth, positive for synaptophysin, chromogranin, CD56, and cytokeratin 7 negative [16]. Stromal carcinoid is an extremely rare malignant ovarian tumor with limited data on clinical features and survival outcomes. In our case, the tumor was restricted to the right ovary and the cyst tissue was totally removed, however the cyst ruptured during the operation. Stage IC 1 right ovary mature cystic teratoma with goitrous carcinoid was diagnosed in the patient. Following the case discussion, it was recommended that the patient be readmitted for right adnexectomy during cesarian section. The majority of women with stage I malignancies as in our case have close monitoring following surgery and may not need additional therapy [2]. However, some stage I cancers, notably extremely big tumors, burst tumors, and poorly-differentiated tumors, are more likely to come back following surgery. Strumal tumors can recur several years after they first appeared, but because they grow slowly, there may still be a high chance of recovery. Surgery can be repeated, and the original chemotherapy regimens can also be utilized to treat a relapse. Recurrence can be treated with hormone treatment [17]. For these reasons, we recommended long-term follow up, for at least five years.

For ovarian cancers, there are no well-structured prevention programs, in recent years many steps forward have been made in this field and new perspectives have been presented as the use of circulating tumor DNA and circulating microRNA profiling. Circulating tumor DNA (ctDNA) is found in primary tumors or metastatic lesions. ctDNA could be extracted by patient's plasma or serum. It can be used as for detecting an early diagnosis and for monitoring the treatment response. It has been reported that if ctDNA persists in treated ovarian cancer survivors it suggests a poor clinical prognosis. Also is seen that it has a higher sensitivity than CA 125. ctDNA's genetic mutations are the same DNA defects of the primary tumor. Thus, the ctDNA detection could be used for early diagnosis and staging of cancer, tumor efficacy evaluation, tumor recurrence monitoring, and prognosis evaluation. Anyhow, more studies are needed in order to confirm the role of this possible new weapon in screening [18].

4. Conclusion

We report the case of a very rare association of an ovarian carcinoid stromal tumor during pregnancy. This case report highlights the diagnostic and therapeutic difficulty of treating ovarian stroma carcinoid, particularly in pregnant women. The primary investigation of choice is ultrasound, however the only way to confirm the diagnosis is by a histological examination. Early diagnosis and intervention can lead to a better prognosis and improved quality of life for the patient. The patient's age and desire for future fertility are important considerations in the decision-making process. These tumors have the characteristics of releasing YY peptide, endocrine dysfunction, steroid hormone secretion, and so on, we should be cautious of the occurrence of this rare malignant tumor of the ovary in female patients with chronic habitual constipation, abdominal colic, diarrhea, abnormal menstruation and crinosity.

Abbreviations

O-RADS

Ovarian-Adnexal Reporting and Data System

CA125

carcinoembryonic antigen

AFP

alpha-fetoprotein

HE4

human epididymal protein 4

CD56

class differentiation 56

Consent

Written informed consent was obtained from both patients for publication of this case report and the accompanying images. A copy of the written consent is available on request to the Editor-in-Chief of this journal.

Ethical approval

The study is exempt from ethnical approval in our institution. Only the patient's authorisation is required.

Written informed consent was obtained from both patients for publication of this case report and the accompanying images. A copy of the written consent is available on request to the Editor-in-Chief of this journal.

Funding

Not applicable.

Author contribution

Drafting the article: Fathi Mraihi, Jihene Basly.

Acquisition of data: Zeineb Ghali, Eya Azouz, Asma Ayari.

Revising the article: Fathi Mraihi, Jihene Basly, Chelli Dalenda.

All the authors have read and agreed to the final manuscript.

Guarantor

Mraihi Fathi.

Research registration number

N.A.

Conflict of interest statement

The authors declared they have no conflicts of interest.

Data availability

Materials described in the manuscript, including all relevant raw data, will be freely available to any scientist wishing to use them for non-commercial purposes.