Struma Ovarii: Clinico-Morphological Features and Therapeutic Experience of a Romanian Institution over 20 Years

Abstract

Struma ovarii is a rare condition with scarce published data regarding clinical, morphological, and therapeutic approaches. This study reports the experience of 25 patients with struma ovarii who received surgical treatment in a gynecology department in Romania. The study was conducted from January 1999 to September 2021 and included patients with confirmed struma ovarii whose medical records were retrospectively reviewed and evaluated. Struma ovarii represented 2.8% of the total number of benign ovarian tumors treated by surgery. The age of the patients was between 24 and 71 years. The tumor was unilateral in 24 cases, 13 cases on the left ovary, 11 on the right side, and bilateral in 1 case. Tumor dimensions ranged between 1 cm and 20 cm. In two cases, the patients had symptoms of hyperthyroidism. The procedure was performed on four women for diagnoses other than an ovarian tumor. In another five situations, there was suspicion of ovarian malignancy. In addition, struma ovarii was associated with other clinical conditions in 22 cases. These lesions represent a diagnostic challenge with heterogeneous clinical and imaging manifestations. Complete information of clinical, morphologic, and surgical findings may improve the diagnostic algorithm and better predict patient outcomes.

1. Introduction

Struma ovarii is a monodermal and highly specialized teratoma that accounts for 0.85 to 1.3 percent of all ovarian tumors [1]. Thyroid tissue is seen in 5–15 percent of benign ovarian teratomas, but the thyroid proportion must be more than 50% of the overall tissue to be classified as a struma ovarii tumor [2,3,4]. Despite the fact that this form of adult teratoma has a varied amount of functioning thyroid tissue, hyperthyroidism is present in about 8% of patients [5,6].

Usually, it is a unilateral tumor [3]. Because of its many distinctive characteristics, struma ovarii has piqued interest since its first description in the early twentieth century; however, many issues remain unsolved at this time. Because of the rarity of this type of tumor, there has been a lack of information in the prior literature about its diagnosis and therapy.

This study presents findings from 25 patients with struma ovarii who underwent surgical treatment after a previous imaging diagnosis of ovarian mass at the First Clinic of Obstetrics and Gynecology Iaşi and aims to define the clinical features, ultrasonographic findings, histological examination, and treatment methods.

2. Material and Methods

Our retrospective study was conducted from January 1999 to September 2021 and included patients with confirmed struma ovarii. Age, clinical symptoms, pre-operative imaging examinations, serum CA-125 levels, post-operative histological diagnosis, and prognosis were all examined in their medical records. Patients were followed up two months after surgery, and those who had unilateral salpingo-oophorectomy were followed up with ultrasonography (US) once a year for three years. In addition, we sent all patients to an endocrinologist for thyroid function tests after histological diagnosis.

The ultrasonographic examination was performed using a vaginal probe with a frequency of 5–9 MHz and, in some cases, an abdominal probe with a frequency of 3–5 MHz.

The surgical approach consisted of unilateral salpingo-oophorectomy for 10 patients, bilateral adnexectomy for 7 cases (for benign tumors on both ovaries), and total hysterectomy with bilateral salpingo-oophorectomy for 8 patients (with other uterus associated pathology or over age 45). All surgeries were made by exploratory laparotomy. The recovery time went efficiently, and thyroid function remained normal. Histopathological analysis was carried out on routinely prepared tissue samples.

All patients supplied their informed consent before enrolment. This study was approved by the Institutional Ethics Board of the “Grigore T Popa” University of Medicine and Pharmacy, Iaşi, and all the authors declared no conflict of interest in connection with this study or its content.

3. Results

The patients’ age ranged between 24 and 71 years, with the highest age of incidence occurring in the fifth decade of life. The tumor was unilateral in 24 cases—(13 cases on the left ovary and 11 on the right side), and bilateral involvement was present in 1 case. Tumor sizes varied between 1 and 20 cm. For 9 patients, tumor size was under 6 cm (

Table 1. Main epidemiological and clinico-morphological data of the study population.

Patient Nr	Age of Patients (Years)	Ovary	The Largest Tumor Size (cm)	Year of Diagnosis	Additional Conditions to Struma Ovarii	CA-125 (Ui/mL)
1	43	left	18	2001	Serous cystadenoma	4.94
2	28	right	4.5	2001	Uterin leiomiomatosis
3	41	right	8	2003	Mucinous cystadenoma	10.7
4	71	right	6	2004	Mucinous cystadenoma	14.6
5	49	left	8	2004	-	3.7
6	51	right	10	2005	Serous cystadenoma Ascites	45
7	35	left	2.5	2005	Ovarian torsion Hyperthyroidism	5.2
8	42	left	1	2005	-	3.1
9	26	left	7	2006	Ovarian torsion	4.2
10	32	left	5	2006	Thyroid papillary carcinoma	22.6
11	45	left	3.5	2007	Uterin leiomiomatosis	9.4
12	33	right	9	2007	Cystic teratoma Chronic inflammation	15.9
13	68	left	9	2007	Surface papilomatosis Peritoneal implants	18.4
14	42	left	4	2008	Teratoma	8.9
15	38	left	7	2009	Teratoma Serous cystadenoma	9.2
16	27	right	6	2010	Pregnancy Serouse cystadenoma	5.6
17	50	left	20	2010	-	3.6
18	46	left	5	2011	Serous cystadenoma	11.2
19	33	right	10	2015	Pregnancy	10.8
20	24	right	8	2016	Mucinous cystadenoma Strumal carcinoid	38
21	42	right	3,5	2018	Teratoma	8.2
22	54	right + left	18	2019	-	4.1
23	31	right	9	2019	Pregnancy Ovarian torsion	6.4
24	54	left	11	2019	Teratoma Hyperthyroidism	11.5
25	59	right	3.7	2021	Strumal carcinoid	19.2

).

Patients with struma ovarii are usually asymptomatic or have non-specific symptoms comparable to those of other ovarian neoplasms. In our investigation, 4 women did not have any symptoms. Lower abdominal pain (n = 10 cases), palpable lower abdominal mass (n = 7 cases), ascites (n = 1 case), and pregnancy with symptoms suggestive of emetic disgravidia and iliac fossa pain (n = 3 cases) were the most prevalent symptoms at the time of diagnosis.

Two patients had a history of thyroid disease, including symptoms and signs of hyperthyroidism, such as weight loss, shaking, palpitations, and sweating. Unfortunately, thyroid function profiles were not carried out before surgery. In four cases, surgery was performed for reasons other than an ovarian tumor (two cases during C-section), and struma ovarii was discovered by coincidence during laparotomy. Pre-operative US raised the suspicion of a malignant ovarian tumor in 5 patients: 1 case was a 51 years old woman with ovarian mass and ascites (Figure 1a,b and Figure 2a,b); 2 cases with many vessels in the core area of the tumor on Doppler examination (Figure 3a,b, Figure 4 and Figure 5) and 2 cases with massive tumors of 18 cm, and 20 cm, respectively, with mixed aspect (solid and fluid mass).

The extent of surgical procedures varied depending on the case: from simple cystectomy unilateral or salpingo-oophorectomy to a total hysterectomy and bilateral salpingo-oophorectomy.

Usually, the gross examination showed a unilateral and solid mass, with a gelatinous, red-brown to green cut surface; goiter-like multinodular or cystic alterations were also seen. The cyst size varied from 1 to 7 cm in diameter, and the cysts were filled with a brown jelly-like material.

Histological examination of struma ovarii revealed variably sized macro and micro follicles often containing pink-staining, homogenous, gelatinous colloid, lined with cuboidal or columnar epithelium (Figure 6 and Figure 7). Follicles were sometimes dilated and separated with thick septa. One particular pattern included prominent micro follicles conveying a pseudotubular appearance, abundant eosinophilic cytoplasm with an oxyphilic appearance. Most patients had birefringent calcium oxalate crystals in the colloid, which are thought to be specific for tumors of thyroid origin.

In teratoma, histological examination revealed mixed tumors containing both solid and cystic areas with different tissues, such as hair, muscle, teeth, bone, or cartilage (Figure 8).

Three cases with histological features of carcinoid tumor (strumal carcinoid) identified in our study had specific neuroendocrine features with insular and trabecular patterns (Figure 9). These cases were not associated with aggressive behavior. The follow-up data did not declare any metastases, recurrence, or relapse.

Struma ovarii in our cases was associated with other conditions such as, mature cystic teratoma (n = 5 cases), serous cystadenoma (n = 5 cases), mucinous cystadenoma (n = 3 cases) (Figure 10), ovarian torsion (n = 2 cases), uterine leiomyoma (n = 2 cases), and peritoneal implants, etc. All conditions mentioned before had a detailed histological evaluation and favorable clinical outcome. The lesions are not predictive factors of aggressiveness for struma ovarii.

Although the majority of cases had benign struma ovarii, one patient had struma ovarii, malignant type. Conventional papillary thyroid carcinoma developed in our single case included a true papillary architecture, lined by simple cuboidal epithelium with clear, “ground glass” nuclei, intranuclear inclusions, and nuclear grooves (Figure 11). This condition had a good correlation and a long clinical course.

4. Discussion

Struma ovarii, first reported by Boettlin in 1889, is an exceptionally rare tumor whose pathogenesis is uncertain. It arises before puberty, but the diagnosis is uncommon during this time [7]. According to the World Health Organization (WHO) definition, thyroid tissue must replace at least 50% of the ovary [3].

Teratomas account for 1–12% of all ovarian tumors, with 0.6% having thyroid tissue zones and just 0.4% being struma ovarii [8]. Other studies reported that 15% of ovarian teratomas contain non-significant thyroid tissue, of which only 0.8% is struma ovarii [9].

Neoplastic transformation occurs in only 5% of all cases [4]. The malignant struma ovarii was first described by Wetteland in 1956 [10]. Because of its numerous distinct characteristics, malignant transformation has piqued people’s interest during the time. In our study, we identified five cases with malignancy suspicion. In one case, tumor ecogeneity and, in particular, extensive vascularization pointed to malignancy. Despite the fact that the IOTA group (International Ovarian Tumor Analysis) has some particular ultrasonographic criteria for struma ovarii suspicion, none of our cases got this diagnosis prior to surgery.

In order to assess the struma ovarii occurrence and identify the risk of its malignant transformation, it is obvious that a long-term follow-up is required. Research in 2008 analyzed 644 patients with diverse unilateral and bilateral ovarian cancers during 11 years, finding ovarian struma in only two cases [11].

4.1. Diagnosis Approach

Location in the right ovary of struma ovarii is infrequent. In the literature, the tumor was described more often on the left side, which was true in our patients. Regarding the dimension of the tumor, Hosseini et al. reported in their study that the tumor sizes ranged from 2.5 to 25.0 cm, which is consistent with our findings [12]. Clinical symptoms that may manifest due to the presence of a struma ovarii are lower abdominal pain (50% of cases), palpable lower abdominal mass, abnormal vaginal bleeding, ascites (one-third of cases), hydrothorax, elevated thyroid function (5–8%), and, rarely, thyroid tumors [13,14]. Except for hydrothorax, all symptoms were present in the participants in our study.

The occurrence of ascites in patients with struma ovarii has been observed to vary, ranging between 17 and 33%, according to several authors [15,16]. The precise mechanisms of ascites formation in patients with struma ovarii is currently unclear, but it has been indicated that if ascites is present, it usually resolves spontaneously after tumor excision. In our study, we had only a single case with ascites.

Struma ovarii is usually non-functional, but 8% can present with thyrotoxicosis, which is likely to be mediated by a mechanism different from classic thyroid hyperthyroidism [5]. It is postulated that struma ovarii is an autonomous hormone-secreting tumor, or thyrotoxicosis, which may be due to autoimmune stimulation of the normal thyroid gland [17].

Our data agree with the study of Casas, showing the same percentage of cases with hyperthyroidism (8%). In our cases, the hyperthyroidism symptoms went away five weeks after surgery.

Even though CA-125 is a non-specific marker for struma ovarii diagnosis, it is required as a laboratory test for every ovarian tumor. However, there are data in the literature proving an increase in CA-125 in the setting of struma ovarii. For instance, in their study in 2009, Mui and Tum described an increased level of CA-125 in only 8 cases of struma ovarii [18]. In our study, we identified two cases of struma ovarii with a CA-125 slight increase of 38 and 45 Ui/ml, respectively; however, these values are lower than those reported in other studies varying between 224–5218 Ui/ml [19]. For this reason, in the differential diagnosis of ovarian formations with high levels of CA-125, struma ovarii should also be considered.

Pre-operative diagnosis is very difficult because US computer tomography (CT) and magnetic resonance imaging (MRI) are not specific enough. With these techniques, we can only see adnexal masses consisting of solid and cystic parts. This is supported by our research, as none of our patients had been diagnosed with struma ovarii prior to surgery. Struma ovarii can be diagnosed using Doppler flow. Blood flow signals detected from the core of the echoic lesion, as well as low resistance to flow, are more common in struma ovarii, but they can also be found in ovarian cancer [20,21]. This US aspect was displayed in two women in our study. It is clear that if we suspect ovarian teratoma and the Doppler exam shows central vascularization, it is almost certainly struma ovarii. In general, struma ovarii appeared as a smooth marginated multicystic mass with high attenuation lesions on precontrast scans on CT [22]. On T1- and T2- weighted images, the cystic spaces demonstrate both high and low signal intensities [23]. Kim et al. revealed that struma ovarii contains a multilobulated complex mass with thickened septa, multiple cysts with varying signal intensities depending on the viscosity of the fluid, and enhanced solid components on MRI [24,25]. Only pre-operative scintigraphy with iodine (¹³¹I) could show active thyroid tissue in the small pelvis. CT, MRI, and scintigraphy were not performed on any of our patients. Because of its rarity, modest traits, and lack of clinical suspicion, struma ovarii frequently goes undetected during intraoperative consultation [26].

4.2. Histopathology Features

The diagnosis of struma ovarii should be considered when evaluating cystic ovarian tumors whose features are not obviously of a specific tumor type. In such problematic cases, immunohistochemical staining for thyroglobulin may be required [27]. Regardless of the histological subtype, this has no prognostic value [3]. Staging and molecular analysis are not relevant for struma ovarii [3].

Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy that occur in struma ovarii; other forms of thyroid carcinoma are rare. Most recently, Roth and Karseladze described a new entity of follicular carcinoma, highly differentiated follicular carcinoma of ovarian origin, characterized by extra ovarian dissemination of thyroid elements (strumosis) with a mild appearance that histologically resembles non-neoplastic thyroid tissue [3,28]. Because of varying usage and the lack of a precise definition, it is recommended that the term malignant struma ovarii no longer be used for cases of malignancy that develop in struma ovarii, except in the generic sense. The term thyroid-type carcinoma originating in struma ovarii (specifying the type) is more appropriate [29]. Our study involved one patient with papillary carcinoma arising in struma ovarii. Our case did not benefit from immunohistochemical analysis because the morphological features of malignancy were clear. The correlation between clinical and malignant histological findings demonstrated a favorable course.

The lack of correlation between morphology and outcome in proliferative and histologically malignant struma ovarii is striking, making the behavior of these tumors particularly unpredictable [30].

4.3. Treatment Strategies

In the case of struma ovarii, surgical treatment is the first option. Because the tumor is usually unilateral and benign, unilateral salpingo-oophorectomy is adequate. Alternatively, if modifications on the contralateral ovary exist and the patient is in pre-or postmenopause, we can perform a total hysterectomy with bilateral salpingo-oophorectomy, as was done in our study.

Thyroid function changes may arise as a complication after struma ovarii ablation in the early post-operative period. Surgical excision is the only treatment for struma ovarii that causes thyrotoxicosis. Antithyroid medicines can be used to remove thyrotoxic symptoms and signs before surgery, and surgery should be scheduled as soon as possible to avoid malignant change. In addition to thionamides, adrenergic blocking medications coupled with iodine, ipodate, or iopanoic acid prevent the T4-to-T3 conversion, may be utilized to allow early surgery [31].

Due to the rarity of malignant struma ovarii, there is a paucity of data regarding the optimal treatment for such patients. Standardized treatment of malignant struma ovarii remains undefined. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy is one surgical option, whereas conservative surgery is another. Currently, the laparoscopic removal of the tumor may be an appropriate treatment option [32,33]. Adjuvant therapy includes external radiotherapy, chemotherapy, thyroidectomy, and radioactive iodine ablation [34].

Fertility-sparing surgery with unilateral salpingo-oophorectomy and preservation of the contralateral ovary and uterus is recognized to be an adequate surgical treatment for germinal cell tumors. If followed by adjuvant chemotherapy, this method may potentially be feasible in premenopausal patients with bilateral illness [35]. The histology result in our case with malignant struma ovarii was unexpected, and we observed no extension beyond the capsule. The treatment was conservative because the woman was 32 years old. Monitoring blood thyroglobulin can be done with better sensitivity in patients with or without thyroidectomy, similar to how it is done in patients with thyroid cancer [36]. Observing successive thyroglobulin levels is the key to early detection of possible recurrence of malignancy.

Early or late pregnancy is a rare clinical setting during struma ovarii evolution [37].

Torsion is the most common and dangerous complication of an ovarian tumor, especially during the 8–16 gestational weeks of pregnancy, and it has been reported to be 10–15%. Tumor rupture is a rather uncommon occurrence. In small tumors with no suspicion of advanced-stage ovarian cancer and total intact removal of the mass is possible, laparoscopic surgery should be used. Because it reduces manipulation of the pregnant uterus during surgery, laparoscopic excision of ovarian tumors in early pregnancy is considered as safe as laparotomy [38]. Our study group included three pregnancy-associated cases with struma ovarii. Even though the tumor was not related to a worse evolution of pregnancy, early detection is mandatory in such situations due to the increased risk of torsion, as mentioned before. We had a case with ovarian torsion at eight weeks of gestation, but the woman delivered at term.

When it comes to struma ovarii and pregnancy, it is important to determine which ovary is the gestational body that supports pregnancy in the first semester. As a result, if the gestational body is on the removed ovary, there is a chance of miscarriage [36].

5. Conclusions

Although unexpected results can also be described, imaging techniques are very useful methods for diagnosing struma ovarii. Still, our research emphasizes the difficulty of diagnosing struma ovarii on the basis of clinical manifestations or imaging studies as the presenting clinical features are widely diverse and may lead to confusion with other lesions. Despite the fact that ovarian struma was linked to a variety of illnesses in our study, surgery was the best option, with long-term patient follow-up demonstrating a satisfactory outcome. Future studies with more cases will be required to determine the most effective tools for an accurate diagnosis.