Malignant Struma Ovarii Τreated With Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Discussion

Struma ovarii is difficult to diagnose on clinical basis and with imaging techniques, mostly discovered incidentally after pathological reprocessing. As in our case, malignant struma ovarii may appear with a picture of clinical mimicry, resembling the most common EOC in advanced stages on imaging with peritoneal carcinomatosis. But even with disease confined to the ovary on preoperative CT with elevated CA-125 levels, it is not possible to differentiate between the much more common histological subtypes as preoperative punctures are outdated methods. Due to the very rare occurrence of hyperthyroidism and the fact that clinically or biochemically manifest hyperthyroidism occurs in less than 5-8% of cases (6), preoperative hormone diagnostics reveal no pathological findings in general. As a result, if no frozen section is performed intraoperatively, the therapy can be identical to epithelial ovarian cancer including HIPEC.

Furthermore, a recent retrospective study of 125 cases found ascites in only 17.6% and elevated levels of CA-125 in 36.4% of the cases (7). Another study of 88 patients found that ascites occurred without evidence of tumor in every patient where cytological reports were available, making preoperative diagnosis even more difficult (8).

At present, no standard guidelines exist for surgical management for malignant struma ovarii (4, 7). In a review by Li et al. unilateral adnexectomy was performed in 33.6% of the cases, 21.6% of patients underwent abdominal hysterectomy with bilateral adnexectomy, and only 17.6% underwent debulking surgery. Bilateral adnexectomy (5.6%) and ovarian cystectomy (8%) were performed in the minority of the cases. Examining the recurrence-free survival (5 year and 10 year RFS 27.1% and 35.2%, respectively) and overall survival, excellent survival rate was found regardless of the surgical management applied (5 year, 10 year, and 20 year OS rates were 95.3%, 88.7% and 88.7%, respectively) (7). As other authors have also suggested, in our treatment decision there was more extensive surgical intervention in case of postmenopausal patients than when fertility prevention is desired at younger patients at a reproductive age (6, 9). Our approach of administering primary systemic chemotherapy within initially not resectable ovarian cancer and performing interval tumor debulking with additional HIPEC was recently confirmed in a study by van Driel (10). Furthermore, application of hyperthermic intraperitoneal chemotherapy was considered in our patient for the reason of suspected peritoneal carcinomatosis to target the microscopic residual disease after surgical elimination of all macroscopic disease, as was also proposed by other researchers (11).

Papillary thyroid carcinoma is the most common type of histology in the published literature (7). Our patient also had papillary thyroid carcinoma, and a struma ovarii originating from the left ovary, which was larger than 12 cm. Robboy et al. suggested, that ≥12 cm struma ovarii in 88% were clinically malignant and in patients with papillary carcinoma this number was 29% (8). Furthermore, papillary carcinoma histology recurred on average of 4 years earlier than follicular adenomatous neoplasms on average of 11 years (8). In addition, an amount of 33% of extraovarian dissemination could be found if the strumal component was larger than 12 cm. In line with this, Shaco-Levy et al. found that ≥10 cm tumor size and ≥80% strumal component were associated with rapid progression and increased lethality (12). On the contrary, in the univariate analysis by Li et al. failed to predict either RFS or OS.

According to the FIGO staging principles involvement of the fibrous cortex of the ovary without penetrating involvement of the serosal surface does not upstage the tumor. At our patient, the malignant papillary tumor was embedded in the ovarian struma, and even this latter portion, which was about 15 cm, showed no capsular penetration.

Robboy et al. indicated the fibrous adhesions as adverse features, as well as presence of ascites and large (≥12 cm) strumal tumor size of the ovary, which are suggestive of extraovarian tumor spread at the time of operation and are likely to recur. These features were all present at our patient with evidence of peritoneal metastasis on the preoperative CT record. Despite the fact that most germ cell tumors are chemosensitive, malignant struma ovarii responds poorly to chemotherapy (7); yet our patient responded well to 6 cycles of neoadjuvant chemotherapy, so that no vital extraovarian involvement was detectable on postoperative histology, only distinct fibrosis and scarring, which were originally peritoneal metastasis. As has been suggested by several authors in the literature, these implants may not be malignant peritoneal implants, but extremely well-differentiated “strumosis” corresponding to normal thyroid tissue (8, 13, 14).

Furthermore, the management of the thyroid gland with thyroidectomy and radioactive iodine ablation after surgical removement of the primary tumor of the ovary is lacking evidence. Some authors recommend routine thyroidectomy followed by an I131 therapy regardless of the presence of metastasis at the time of diagnosis to avoid local recurrence and distant metastases (6, 15-17). This indication may be questioned since thyroid metastases from extrathyroidal primary tumors are rare and in unselected autopsy series, thyroid metastases were detected in approximately 1% of the cases (18, 19). If extraovarian metastases are present, these usually originate from differentiated thyroid neoplasms, such as papillary carcinoma or follicular carcinoma, and occur in peritoneum, lymph nodes, liver, lung, bone, and brain with manifestation of ascites or pleural effusion (5, 17, 20-22).

According to the German guidelines, surgical removal of thyroid metastases is indicated for extrathyroidal primary tumors if the metastasis is histologically proven or there is diagnostic evidence for it. For this, a local and systemic staging is required (23, 24). Our decision was in line with other researchers, who claim that intraabdominal surgical removal of the ovarian tumor and its implants is sufficient, and thyroidectomy and radioiodine therapy are only indicated in the case of metastasis or recurrence (25-27). The indication for thyroidectomy should, therefore, be made within the framework of the interdisciplinary therapy strategy.

In summary, malignant struma ovarii is a very rare histotype of the ovary, which is diagnosed in the vast majority of cases postoperatively and histologically. Due to its rarity and the fact that there is no consensual therapy, multidisciplinary treatment with individualized therapeutic plan involving gynecological oncologists, endocrinologists, surgical oncologists, and nuclear medicine specialists is required. Regular follow-up for at least a decade is recommended since recurrence intervals are quite long (8).