Teratoma combined with struma ovarii and sarcomatoid carcinoma: a case report and review of the literature

Abstracts

This is a rare case of struma ovarii combined with sarcomatoid carcinoma. Because struma ovarii and ovarian sarcomatoid carcinoma have an extremely low incidence, this may be the first case of a combined occurrence of both. Therefore, this report describes its clinical manifestations, diagnosis, and treatment, analyzes the pathogenesis, and summarizes the previous literature in the hope that it can be helpful to other tumor-related medical personnel and provide material support for the formation of guidelines for this disease.

Introduction

Ovarian teratoma is a kind of ovarian germ cell tumor with mainly benign lesions, accounting for about 15% of the total number of primary ovarian tumors, and its malignant change rate is only 0.2% ~ 2%, and mainly squamous cell carcinoma [1]. Struma Ovarii (SO) is a special pathological type of teratoma differentiated from a single germ layer, accounting for about 2% ~ 3% of ovarian teratoma and 0.1% ~ 0.5% of all ovarian tumors [2], incorporation with sarcomatoid carcinoma is even rarer. Therefore, the clinical diagnosis, treatment plan, and prognosis evaluation of Struma Ovarii with sarcomatoid carcinoma are still unclear, and it is difficult to form a convincing expert consensus or guidelines for gynecologic oncologists. This paper reported a case of ovarian teratoma combined with struma ovarii and sarcomatoid carcinoma, summarized its clinical characteristics and treatment methods in the light of the literature, in order to improve the relevant knowledge of the disease and provide a reference for the diagnosis, treatment, and prognosis.

Case presentation

A 67-year-old woman was admitted to the hospital with "the lower abdomen was unwell for more than half a year, and the pelvic mass was found for 5 days". In May 2023, she felt abdominal discomfort and occasionally had abdominal pain. She took oral antibiotics for more than half a month (The patient self-medicated, which could only be determined to be a second-generation cephalosporin), and abdominal pain was slightly relieved. In June 2023, there was more pain in the lower abdomen than before and she went to the local hospital for treatment. Physical examination showed that vital signs were stable, generally in good condition, and no abnormal physical development. There was no palpable enlargement of superficial lymph nodes throughout the body and no abnormalities on cardiopulmonary auscultation. The abdomen was flat without tenderness and rebound pain, the liver and spleen were not palpable under the ribs, and there was negative shifting dullness. The gynecological examination revealed normal vulvar development, with notable thickening and hyperpigmentation of the left labia and perineal skin junction. The patient had a patent vagina, a smooth cervical posterior lip, and an erosion cervical inner anterior lip. The uterus was unsatisfactory on palpation, no mass was touched in the left appendage area, and the mass in the right appendage area was about 9 × 7 × 7 cm in size. The rectal mucosa was smooth and nodules were not touched in the Douglascul-de-sac.

On December 18, 2023, an ultrasound at a local hospital suggested multiple pelvic masses; Magnetic resonance imaging (MRI) of the pelvis showed a right adnexal mass (9.8 × 6.3 cm, mixed-signal) suggestive of a possible teratoma; there was also a enhancing nodule, so malignancy could not be completely excluded (Fig. 1a and b). On December 25, 2023, she came to our hospital for further treatment. The patient had no fever recently, and her diet, sleep, urinary, and bowel function were normal. She had regular menstruation previously, with natural menopause at 51 years old, G2A0P2, VD. Past medical history and family history of tumor were denied.

Fig. 1

a depicts a pelvic magnetic resonance T1W enhanced fat suppression image, which reveals a visible left pelvic cystic-solid interphase mass. b is a diffusion-weighted (DWI), which indicates a high signal of tumor nodules in the right posterior area of the tumor. The O-RADS MRI score is 4, indicating a high probability of malignancy. c and d show an irregular mixed mass on the right side of the pelvic cavity, with visible fat density and calcification, and enhanced soft tissue components,  indicating the presence of solid component

The routine blood test and liver and kidney function results were normal. Tumor markers were of the normal range: CA199 3.51 U / mL; AFP 4.33 ng/mL; CEA 2.08 ng/mL; CA125 26.40 U / mL; HE422.70 pmol / L. HPV: (-); TCT: NILM. ECG: Normal. Cardiac ultrasound: in the resting state, the left ventricular overall systolic function is normal. Pulmonary function test: moderately restricted ventilation dysfunction, mild ventilation dysfunction, and reduced small airway function. Computed tomography (CT) of the lung and abdomen: irregular mass on the right side of the pelvic cavity, ranging about 9.1 cm × 6.7 cm, mixed density, fat density and calcification, and enhancement of soft tissue composition; no enlarged lymph nodes in the retroperitoneal area (Fig. 1c and d).

After a comprehensive examination, the preliminary diagnosis of pelvic mass (malignancy cannot be excluded). After the evaluation by anesthesiologists of our hospital, there were no absolute surgical contraindications, and the exploratory laparotomy was performed under general anesthesia on December 27, 2023. Intraoperative observation: no ascites, no abnormality in the upper abdomen. The right ovary was replaced by a mass, about 10 × 8 × 7 cm in size, and the right fallopian tube was attached to the mass; the appearance of the left ovary and fallopian tube was normal. No significant abnormalities were observed in the uterus and greater omentum appearance.

The peritoneum of the bladder wall layer was adhered to the right ovarian mass with an area of about 4 × 3 cm. After separation, the abnormal peritoneal membrane was completely removed and sent to intraoperative frozen pathology. The result showed that the heterogeneous cells were seen in the fiber stroma, which was considered carcinoma. The right ovarian vessels were isolated by high ligation, the right broad ligament was freed, the right utero-ovarian ligament was isolated, and the right ovary and fallopian tube were completely removed and sent for intraoperative frozen pathology. The result was (right adnexal mass) struma ovarii and the diffuse distribution of heterogeneous cells in some areas was malignant. Based on the results, the intraoperative diagnosis of ovarian cancer was stage IIB, according to the 2023 NCCN guidelines for ovarian cancer [3]. Then, the uterus and left ovary fallopian tube, greater omentum were completely resected, with peritoneal multipoint biopsy.No enlarged lymph nodes were found in the internal iliac, external iliac, common iliac, or obturator regions, so no resection was performed.

After surgery, the gross specimen was examined as follows (Fig. 2a); upon dissection of the mass, a cystic-solid component was visible within the right ovary, with contents including oil, hair, bone structure, and thyroid components (Fig. 2b).

Fig. 2

a shows the gross specimen (en -bloc); b shows upon dissection of the specimen, which is a cystic-solid component, with contents including oil, hair, bone structure, and thyroid component

Postoperative pathology showed that the morphology was dominated by a teratoma component with polygonal differentiation and prominent zones of heterogeneous spindle cells, which had a clear line between the two regions (Fig. 3), and tumor cell infiltration could be seen under the peritoneum of the bladder wall (Fig. 4). The teratoma component exhibited mature thyroid follicular structures (a variable amount of eosinophilic colloids was observed within the cavity, with the follicular epithelium was a single layer of low columnar or cubic cells), and it accounted for > 50% of the tumors, and differentiated and mature squamous epithelium and skin appendages (sebaceous gland and hair follicle structures) can also be found; the spindle cell region was characterized by significant cellular heterogeneity, deeply stained nuclei, and eosinophilic cytoplasm. The immunohistochemical results were as follows CK ( +), Vimentin ( +), Ki67 (80% +), S-100 (-), Desmin (-), MyoD 1 (-), P53 ( +) / mutant, P40 (-), Sall-4 (-), Pax-8 (-), SMA minority cells ( +), the data indicated that this region had an epithelial and mesenchymal origin of biphasic differentiation and did not support differentiation into nerve, striated muscle, female germ cell tumors, and squamous cell carcinoma (Fig. 5a-d).

Fig. 3

HE staining shows that the morphology is mainly composed of teratoma components, with polygonal differentiation and obvious heterogeneous spindle cell regions, with clear boundaries between the two regions

Fig. 4

HE staining shows infiltration of bladder serosa by cancer cells

Fig. 5

a Under low magnification, epithelial derived marker CK is expressed in both the follicular of the thyroid gland and atypia spindle cell region (Envision two –step method); b Under low magnification, the mesenchymal derived marker Vimentin is not expressed in the thyroid follicular region, but in the spindle cell region (Envision two step method); c Under low magnification, the squamous epithelial marker P40 is not expressed in the spindle cell region, ruling out squamous cell carcinoma, which is the most common malignant transformation of teratoma; d Under low magnification, the proliferation index Ki67 is low expressed in the thyroid follicular region and high expressed in the spindle cell region, which means higher degree of malignancy in sarcomatoid carcinoma

TC chemotherapy is the recommended postoperative treatment. The patient is currently on chemotherapy with no adverse reactions above II°.

Discussion

Ovarian teratoma was classified into mature teratoma (benign) and immature teratoma (malignant) according to their pathological nature, 95% of which were mature teratoma [4]. Early symptoms are not obvious, mainly due to the physical examination found, surgery is the main treatment currently [5]. SO is a highly specific monoembryonic teratoma, whose diagnostic criteria are microscopic thyroid tissue composition > 50%, or thyroid tissue < 50% but with significant hyperthyroidism, or visually recognizable thyroid tissue in a mature teratoma [6]. SO has predominantly unilateral, left-sided onset, with right-sided onset in slightly older patients and bilateral onset in 8% of patients [7]. The right-sided onset of the disease in this elderly patient is consistent with the literature. The clinical incidence of SO is very low and lacks typical clinical symptoms. Most of them are found by physical examination or with abdominal mass or abdominal pain. However, some studies have reported that about one-third of clinical patients have "Meigs syndrome" [8]. Based on the high incidence of pleural effusion and ascites and high level of CA125 expression in struma ovarii, some experts suggest that pleural effusion, ascites, and elevated CA125 should be included in the differential diagnosis of pelvic mass and struma ovarii [9]. However, CA125 will increase in both benign and malignant cases, and will not continue to rise even in malignant cases. It is speculated that the increase in CA125 is not a direct result of the tumor itself, but rather a side effect of ascites [10]. In a recently published case report of a papillary thyroid carcinoma within a mature cystic ovarian teratoma, CA25 was also found to be in the normal range [11]. It is worth noting that although SO is a tumor composed of thyroid tissue, only 8% of the patients have hyperthyroidism [12]. This suggests that, in the majority of cases, the thyroid tissue in the SO does not have the full function of synthesizing thyroid hormones. And some studies have shown that thyroglobulin can be used as a diagnostic reference for SO [13]. In this case, thyroid function was not tested because SO was not diagnosed preoperatively and the patient did not have symptoms of hyperthyroidism.

Because the clinical features of SO are also similar to those of ovarian malignancies, so preoperative imaging diagnosis becomes more important to distinguish ovarian cancer and avoid cancer-type surgery (eg, bilateral salpingectomy, hysterectomy). Ultrasound is the first choice for the evaluation of ovarian masses during imaging studies [14]. However, the ultrasound findings of struma ovarii are ambiguous and usually manifest as a multilocular cystic ovarian mass with solid components of various amounts, the ultrasound typically demonstrates these non-specific heterogeneous solid cystic features [15]. The SO has features overlapping with those of malignant ovarian epithelial tumors, though they both present as a unilateral complex adnexal mass often associated with ascites, or as multi-cystic mass with solid components and multiple cystic locules, usually including teratoma components. The SO contains a”struma pearl”: a rounded solid area with smooth contours corresponding to colloidal thyroid tissue [16]. Familiarity with the "doughnut sign" and the "fat layering sign" can help in the differential diagnosis, but it is possible to overestimate the malignancy of SO [17]. MRI shows a solid component with moderate to high signal intensity on T1-WI, whereas the signal intensity of the cystic portion on T2-WI depends on the viscosity of the fluid. On CT, the enhancement of the septal or solid component depends on the content of the thyroid tissue [18, 19]. As SO is an uncommon tumor, unlike the most common types of teratoma, does not demonstrate lipid material on either CT or MRI [20], but 123I or 131I scintigraphy is useful for diagnosing a superfunction SO [18]. Because SO is difficult to make a definitive preoperative diagnosis, postoperative paraffin pathology combined with immunohistochemistry is still the ultimate basis for diagnosis. In addition to thyroid tissue, there was obvious mature teratoma tissue [21], typical presentation: multilocular, uneven wall thickness, yellow and grayish-red jelly-like contents; immunohistochemical features: TTF 1 ( +), TG ( +), PAX-8 ( +), CK7 ( +), and Muc-1 ( +). Routine gynecological examinations (especially ultrasound scans) improve the early diagnosis of SO. Due to the low incidence of SO and no clear diagnosis and treatment guidelines, surgery is still the main treatment modality. Due to its ultrasound morphology, which is quite similar to that of malignant ovarian carcinoma, most SO cases are often operated on with laparotomy, involving either ovariotomy or oophorectomy [22]. For malignant struma ovarii, radioactive iodine supplementation after surgery is effective in preventing metastasis or recurrence [23]. For people at high risk of developing cancer-causing factors, postoperative clinical and ultrasound follow-up is needed every six months or year.

In addition to teratoma and SO of the pathological components, some malignant cells also be found that have significant spindle shape changes, including both epithelial markers and sarcoma markers. At first, we thought it was carcinosarcoma. However, carcinosarcoma needs to determine the components of carcinoma, such as adenocarcinoma, and squamous carcinoma. Sarcomatoid carcinomas typically feature pleomorphic spindle cells in intertwined bundles with high-grade nuclei, expressing both epithelial (e.g, CK, EMA) and mesenchymal (e.g, Vimentin) markers. They lack tissue specificity, excluding sarcomas like liposarcoma and rhabdomyosarcoma, as well as carcinomas like ovarian plasma carcinoma and squamous cell carcinoma, thus qualifying as sarcomatoid carcinoma [24]. The specific origin of the cancerous and sarcomatous components could not be determined in this case. The protein P40, which characterizes the most common squamous carcinoma of teratoma malignancy, is negative. However, it expressed both epithelial (CK) and mesenchymal component (Vimentin) markers, so pathologists prefer to diagnose sarcomatoid carcinoma. SC is also known as spindle cell carcinoma, which the epithelial carcinoma component determines the biological behavior of metastasis, and the sarcoma component determines the prognosis. Usually, sarcomatoid tissue accounts for more than 50% of malignant tissues [25]. In addition, it is necessary to perform immunohistochemistry to confirm the presence of epithelial components or sarcomatoid tissue surrounded by epithelial tissue that has a heavy heterogeneous proliferation of carcinoma in situ. Otherwise, it should be differentiated from sarcoma, to avoid misdiagnosis when the proportion of sarcoma components in SC tissue is too large [26].

Whether it is carcinosarcoma or sarcomatoid carcinoma, for germ cell tumors, which may have the characteristics of cell stemness, there are currently three theories of its formation mechanism: collision theory, combinatorial theory, and transformation theory. "collision theory" believes that these two types of diseases have two components: epithelial cancer and sarcomatoid stroma, so it is proposed that tumor cells are biclonal, epithelial cancer components and sarcoma components are derived from two types of stem cells, evolve independently, and then collide; the "combination theory" suggests that a stem cell precursor in the early bidirectional differentiation into epithelial carcinoma components and sarcoma components; at present, the most recognized "transformation theory" proposes that the sarcoma component comes from carcinoma cells or the original stem cells is differentiated into one kind of cell and re-differentiated to form a second cell. Its essence is a special type of cancer, and the sarcomatoid component is only the transformation of the cancer component [27]. A recent study tested RNA for cancer and sarcoma components in 18 patients with ovarian carcinosarcoma (OCS) found that the cancer component in OCS was more mesenchymal compared to epithelial ovarian cancer, supporting the conjecture that the sarcoma component is transformed through epithelial-mesenchymal cancer component. In this case, CK ( +) and Vim ( +) suggested that the spindle cell area was characterized by biphasic differentiation characteristics of epithelial and mesenchymal origin, which also tended to support the "transformation theory" [28].

Although sarcomatoid carcinoma has been found in several organs, including the breast, bladder, and kidney [29,30,31], there are few clinical reports and studies on ovarian sarcomatoid carcinoma (OSC) and only a few documents on PubMed, and most of them are case reports [32, 33]. There are no standard guidelines for their diagnosis and treatment currently. Combined with the existing literature and our clinical experience, the early symptoms of OSC are not obvious, and they are usually found in physical examination or abdominal pain, abdominal distension, and other manifestations. Tumor markers generally increase in CA125, and then the pelvic mass is found by imaging examination. Preoperative imaging does not allow for differential diagnosis. However, the extent and staging of the disease can be assessed. Ultrasound cannot differentiate ovarian sarcomatoid carcinoma from other poorly differentiated ovarian cancers. CT can provide the condition around the lesion and the presence of peritoneal and lymph node metastasis, providing an important basis for clinical staging. MRI shows mixed images of hemorrhage, cyst, or necrosis [34]. Due to the difficulty of preoperative diagnosis of OSC, it is finally determined by postoperative pathological examination, as a result, the condition has often progressed to advanced stages when identified. In this case, the diagnosis of teratoma was initially confirmed by preoperative imaging, which prompted the patient to seek further treatment at our hospital. Although the preoperative imaging could not further confirm the diagnosis, it still plays an important role. This suggests that with the existing medical technology, although we cannot accurately diagnose teratoma combined with ovarian struma and sarcomatoid carcinoma, we can make good preoperative preparations for malignant tumor during the patient's operation if teratoma is diagnosed, which is very meaningful. There is no direct relevant literature for the evaluation of prognosis, which can refer to the latest literature report on ovarian carcinosarcoma, whose 5-year survival rate is 29.8%, and the median survival period is 16 to 24 months [35]. Median survival was reported to be 11 months for patients with sarcomatoid carcinoma of the bladder and 3.5 months for patients with sarcomatoid carcinoma of the rectum [36, 37].

Currently, the treatment of OSC is based on cytoreductive surgery combined with platinum-based chemotherapy, similar to ovarian carcinosarcoma or epithelial carcinoma [38]. Among other treatments, radiotherapy is not recommended, and the efficacy of targeted therapy and immune checkpoint inhibitors for OSC is still controversial and needs more studies [39, 40]. Aoki M et al found that the loss of expression of the ARID1A gene and the same PIK3CA mutation in different tissues, proving the monoclonality of sarcomatoid carcinoma and also providing evidence to support the transformation theory [41]. According to the monoclonality of the disease, individual treatment options can be selected for the mutation gene to improve the survival rate and improve the quality of life for patients.

Conclusion

We report a rare case of ovarian tumor in which preoperative investigations showed a high likelihood of benignity, but malignancy could not be completely excluded. Intraoperative frozen section pathology revealed a malignant component. According to FIGO staging, the diagnosis was stage IIB, and total hysterectomy + double adnexa + greater omentum was performed. Postoperative pathology diagnosed teratoma combined with struma ovarii and sarcomatoid carcinoma. According to our case and published literature, in patients with teratomas of old age and large local foci, attention should be paid to the possibility of sarcomatoid carcinoma in addition to the possibility of malignant teratoma. It is important to achieve complete excision of the tumor and avoid rupture during surgical treatment to prevent metastasis or spread.

Limitations

(1) Although the patient was initially diagnosed with teratoma by color ultrasound and MRI, the patient had no history of thyroid disease or hyperthyroidism symptoms. Therefore, the relevant test was not carried out, and the struma ovarii was not diagnosed before surgery; (2) Up to now, the observation time is short, and the final survival and outcome still need to wait; (3) Genetic testing should be helpful to the diagnosis and treatment of this disease, but because its consumption is not covered by the Chinese medical insurance, so not be given to patients. In the future, we plan to seek funding for genetic testing to uncover more insights into the pathogenesis at the genetic level.