Abstract

Struma ovarii is a monodermal variant of ovarian teratoma. Thyroid-type carcinoma arising in struma ovarii is rare. The most common type is papillary carcinoma, followed by typical follicular carcinoma. A 75-year-old hypertensive patient consulted for the sensation of a painless pelvic mass that has been progressing for six months. The abdominopelvic ultrasound showed a right lateralized abdominopelvic mass measuring 14x13x8 cm with a solid and cystic double component. The patient underwent a unilateral right adnexectomy. Grossly, the tumor was encapsulated and lobulated. On cut sections, it was solid brown whitish in color and gelatinous. On histological examination, it was formed of follicular structures of variable size filled with a dense colloid. From this goiter a malignant tumor proliferation arose, arranged in sheets, trabeculae and follicular structures, and the tumor cells were cubic or polyhedral moderately atypical with few mitotic figures. There were no papillary-like nuclear features. There was focal capsular and vascular invasion. Immunohistochemical study showed positive immunostaining of tumor cells with TTF1. Postoperative course was uneventful. The exact prognosis of thyroid-type carcinoma arising in struma ovarii is still unclear because of its rarity, inadequate follow-up, and the absence of consensus in diagnosis and treatment.

Introduction

Struma ovarii is a rare monodermal variant of teratoma. It is composed predominantly of thyroid tissue (50%), and accounts for approximately 2.5 to 5% of ovarian teratomas 1,2. Malignant struma ovarii is very rare accounting for less than 5% of the cases. Papillary and follicular carcinoma are the most frequent types of malignancy that arise in struma ovarii; other forms of thyroid carcinoma occur rarely 1,2.

In this paper, we report a new case of follicular carcinoma arising in struma ovarii. Our aim was to recall the clinicopathological features of this rare entity.

Clinical history

A 75-year-old hypertensive patient consulted for the sensation of a painless pelvic mass that has been progressing for six months. The abdominopelvic ultrasound showed a right lateralized abdominopelvic mass measuring 14x13x8 cm with a solid and cystic double component. The patient underwent a unilateral right adnexectomy. On gross examination, the tumor was encapsulated and lobulated (Fig. 1 A). On cut sections, it was solid brown whitish in color and gelatinous (Fig. 1 B). Intra-operative frozen section analysis was performed and concluded to an adult type granulosa cell ovarian tumor. Subsequently, the patient underwent total abdominal hysterectomy with bilateral salpingo-oopherectomy, without adjuvant treatment. On histological examination, the ovarian mass was formed of follicular structures of variable size filled with a dense colloid. From this goiter a malignant tumor proliferation arose, arranged in sheets, trabeculae and follicular structures (Fig. 2 A, B). The tumor cells were cubic or polyhedral moderately atypical with few mitotic figures (Fig. 2 C). There were no papillary-like nuclear features (Fig. 2 C). We noted focal capsular and limited vascular invasion < 4 vessels (Fig. 3 A-D). Immunohistochemical study showed positive immunostaining of tumor cells with TTF1 (Fig. 2 D). The final pathological diagnosis was malignant struma ovarii with minimally invasive follicular carcinoma. By analogy to follicular carcinoma of the thyroid, this follicular carcinoma arising in struma ovarii can be classified as minimally invasive with limited vascular invasion < 4 vessels.

Postoperative course was uneventful. After the operation, thyroid function tests and the thyroglobulin level were assessed. Thyroid stimulating hormone and free levels of thyroid hormones and thyroglobulin were within normal limits. The patient did not receive any adjuvant treatment. During the six-month follow-up period, the patient did not show evidence of recurrence or metastasis.

Discussion

Struma ovarii is a benign and relatively uncommon monodermal germ cell tumor with less than 200 cases reported in literature 3-5. It can occur at any age, with a peak of frequency in the fifth and sixth decades of life 6. Patients with follicular carcinoma arising in struma ovarii range from 22 to 70 years old 7. The most common presenting symptom of struma ovarii is a pelvic mass as was the case in our patient. Ascites has been reported in 15-20% of cases, but the presence of ascites does not necessarily indicate malignancy. Although struma ovarii is a neoplasm consisting of thyroid tissue, only 8% of patients present with hyperthyroidism 8. The term struma ovarii should be reserved for tumors composed either exclusively or predominantly of thyroid tissue (> 50%) 9. Struma ovarii also comprises cases of mature teratoma with less than 50% thyroid tissue that contain thyroid-associated malignancy 9. The most common malignancy arising in struma ovarii is papillary thyroid carcinoma followed by follicular carcinoma 10. Recently, some authors described a new entity, highly differentiated follicular carcinoma of ovarian origin, which is characterized by extra-ovarian dissemination of thyroid elements with an innocuous appearance that histologically resembles non-neoplastic thyroid tissue 11. To the best of our knowledge, approximately 50 cases of malignant struma ovarii with follicular-type carcinoma have been reported in the English language literature 12. Because of its rarity, there has been disagreement regarding the diagnosis and the treatment of malignant struma ovarii. Some authors have advocated that the histological diagnosis of malignant struma ovarii should follow the same guidelines as those for thyroid carcinomas 1.

The histological diagnosis of malignant struma ovarii with follicular carcinoma is often difficult, since it is frequently challenging to evaluate capsular invasion in the ovary. In these cases, the diagnosis of malignant struma ovarii is based on the evidence of malignant behaviors including the presence of vascular invasion, dissemination, or metastasis. The most reliable diagnostic criterion for follicular carcinoma is vascular invasion in struma ovarii. Adequate sampling is therefore crucial in this setting 11. Histological changes of malignancy in struma often do not equate with clinically malignant behavior, and most cases of thyroid-type carcinoma arising in ovarian struma do not have a clinically aggressive course 9. According to some authors, the identification of a specific molecular alteration in malignant struma ovarii with follicular carcinoma can be a useful biomarker for the prediction of malignant behavior of malignant struma ovarii with follicular carcinoma even when confined to the ovary. In one study, the authors investigated the tumor samples of malignant struma ovarii with follicular carcinoma for 50 cancer-related genes, including RAS, BRAF, p53, and PPARgPAX8 gene fusion by targeted DNA sequencing and fluorescence in situ hybridization, respectively. The main driver gene alterations in follicular thyroid carcinoma were not found in malignant struma ovari, which suggests the possibility of a different mechanism of tumorigenesis for malignant struma ovarii with follicular carcinoma 12. The histological differential diagnosis of struma ovarii includes metastatic thyroid carcinoma to the ovary, stromal carcinoid, sex cord stromal tumor and melanoma.

The treatment of choice of malignant struma ovarii is contraversial. Management strategies include radical surgery with or without thyroidectomy, followed by adjuvant therapy (chemotherapy, external radiotherapy, thyroid suppression) 13. Some authors have advocated that malignant struma ovarii should be treated with total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvicparaaortic lymph node sampling and thyroidectomy followed by I131 therapy 6. According to these authors, thyroidectomy should be a part of radical surgery to exclude the possibility of a primary thyroid carcinoma 6.

The prognosis of thyroid-type carcinoma arising in struma ovarii is still unclear because of its rarity, inadequate follow-up, and the absence of consensus in diagnosis and treatment. However, limited case reports and a small-series review demonstrated a good prognosis.

Roth et al. 10 concluded that anaplastic carcinoma is the most aggressive tumor type, and highly differentiated follicular carcinoma of ovarian origin is the least aggressive. Of the more common tumor types, typical follicular carcinoma is more aggressive than papillary carcinoma. However, the conclusion that typical follicular carcinoma is more aggressive than papillary carcinoma is still not convincing because of the rarity, the limited case reports, and the variability between median and mean survival data 7. Further investigation and studies with more cases are needed to reveal the survival difference between follicular and papillary carcinoma 7,10.

The metastatic potential in patients with struma ovarii is low. The most common metastatic sites include other pelvic structures, contralateral ovary, omentum, and mesentery 14. In rare cases, thyroid tissue may spread to the peritoneal cavity in a condition termed peritoneal strumosis 15. The peritoneal implants grow slowly and only rarely cause side effects such as the formation of adhesions and intestinal occlusion. Pathologic examination of the peritoneal implants shows multiple nodules of mature thyroid tissue of various sizes with features similar to those of struma ovarii 7.

In conclusion, malignant struma ovarii remains a challenge for the clinicians. Although prognosis of malignant struma ovarii is favorable, its clinical course is unpredictable and consensus on its optimal treatment has not been clearly established. We need more data to determine the optimal diagnosis, management and follow-up protocols for this rare entity.

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