Malignant Struma Ovarii—Management and Follow-up of a Rare Ovarian Tumor: A Case Report

INTRODUCTION

Germ cell tumors are derived from the primordial germ cells of the ovary and account for 20–25% of all benign and malignant ovarian neoplasms of germ cell origin.¹ Mature cystic teratomas (commonly known as “dermoid cysts”) are the commonest germ cell tumors and predominantly found in young women of age group 30–40 years. It accounts for about 30–45% of all ovarian neoplasms and around 60% of all benign tumors arising in the ovary with a 0.17–1.4% reported incidence of malignant transformation. Teratomas are composed of well-differentiated derivations from at least two of the three germ cell layers (ectoderm, mesoderm, and endoderm) and about 10% of tumors are bilateral.² Most of the patients with dermoid cysts are asymptomatic and it may be discovered accidentally during gynaecologic investigations for other conditions or due to mass effect. When it is discovered during the reproductive age group, cystectomy is indicated. However, if discovered in postmenopausal age, the likelihood of malignant transformation of any of the components is very strong.³ It is the most common ovarian tumor removed during gynecological surgery.^4,5

Most mature cystic teratomas are unilocular, and filled with sebaceous material. The cyst wall is lined by squamous epithelium which is thin and compressed, often hyalinized ovarian stroma covers the external surface.^6,7 Ectodermal tissue (skin derivatives and neural tissue) is invariably present. Hair follicles, skin glands, and muscle lie within the wall. There is usually a raised protuberance projecting into the cyst cavity called the Rokitansky protuberance or nodule. Most of the hair arises from this protuberance. Whereas bone or teeth when present, tend to be located within this nodule.⁸

The mesodermal (fat, bone, cartilage, muscle) and endodermal components (gastrointestinal and bronchial epithelium, thyroid tissue) are also seen in the majority of cases.² Adipose tissue is present in 67–75% of cases, while teeth are seen in 31%.^2,6,8

Struma ovarii is a rare monodermal variant of ovarian teratoma accounting for only 2% of all mature teratomas. To be classified as a struma ovarii, teratoma must be composed of >50% of mature thyroid tissue.^9,10 It is usually a benign condition, but the malignant transformation is observed in about 5% of cases.^11,12 Hyperthyroidism may be present in 5–8% of cases, while thyroid cancer is present in less than 5% of all struma ovarii with metastasis in 5–23% of malignant struma ovarii patients.^13,14

We report a case of malignant struma ovarii with a focus on papillary thyroid cancer in mature cystic teratoma which was diagnosed at an early stage (stage IA) and was managed appropriately.

CASE DESCRIPTION

We present a case of a 48-year-old perimenopausal female, para 4 live 4, presented in the outpatient Department of Obstetrics and Gynaecology, Jawaharlal Nehru Medical College and Hospital with the complaint of pain in the lower abdomen for 3 months. Her past medical history was uneventful and her menstrual history was normal. Her general condition was fair. There was no visible or palpable evidence of any neck swelling, breast abnormality, or lymphadenopathy. Her per abdominal examination showed a midline, large 14 weeks size, cystic, non-tender, well-defined, freely mobile (side to side) mass arising out of the pelvis. Her pelvic examination revealed a mass on the left side with a normal-sized uterus, with loss of intervening space and moving with cervical movement. Per rectal examination ruled out any nodularity in POD. Routine and specific investigations were carried out. USG’s whole abdomen demonstrated a large cystic (79 × 72 × 75 mm) mass arising from the left side adnexal region, the lesion was thin-walled and showed mixed echogenicity with the sedimentation of echogenic material and few hyperechoic calcified foci likely ovarian dermoid cyst. CA 125 was 26 U/mL. Given clinical, radiological, and biochemical findings, the patient was taken for laparoscopy.

Her intraoperative finding revealed a left-sided cyst ovarian mass of 72 × 80 mm size. Left-sided salpingo-oophorectomy was performed, cyst was drained in a bag without any peritoneal spillage, whole ovary with cyst along the fallopian tube was taken out from the port, and tissue was sent for HPE (Figs 1 to 3).

Histopathology report showed a mature cystic teratoma with struma ovarii with developing papillary thyroid carcinoma. The immunohistochemistry showed >75% of tumor cells with diffuse CK-19 positivity compatible with patient care technician (PCT). The fallopian tube was histopathologically unremarkable (Fig. 4).

Further management was discussed with the Gynec Oncologist, and she was advised to stage laparotomy with thyroidectomy for confirmation of disease, but she refused thyroidectomy. On staging laparotomy, intraoperative findings were as follows, the right-side tube, ovary, and uterus were normal. There was no fluid in the peritoneal cavity. Peritoneal surfaces, omentum, bowel, liver, and diaphragm all were normal. Peritoneal washings and liver and diaphragm surface biopsies were sent for cytology. A total abdominal hysterectomy with right-sided salpingo-oophorectomy with bilateral pelvic and para-aortic lymphadenectomy with omentectomy was performed. No malignant cells were seen in cytology. The histopathology of the right ovary, tube, uterus, lymph nodes, and omentum was normal, and surgical staging IA was assigned. The postoperative course was uneventful.

Thyroid function tests and the thyroglobulin level were also evaluated. Thyroid-stimulating hormone was suppressed and free levels of thyroid hormones and thyroglobulin were in normal ranges. Thyroid ultrasound scanning was also normal. She has been free of the disease for the last 2 years.

DISCUSSION

Mature cystic teratoma (MCT) is most prevalent germ cell tumor in women of reproductive age and responsible for 20% ovarian neoplasm.¹⁵ They are often discovered incidentally on physical or sonographic examination. They may contain hair, teeth, or bone and fatty material. Malignant potential of an MCT is less than 2% of all mature dermoid cysts. Struma ovarii a very rare histological diagnosis is found in just 3% of ovarian teratomas, 2% of all germ cell tumors, and 0.5% of all ovarian tumors.^16,17 Malignant transformation is uncommon, in only about 5% struma ovarii.^16,18

Malignant transformation starts in the postmenopausal period mostly in the 5th and 6th decade with a median age of 55 years; the common malignant transformation occurs in squamous cell carcinoma, adenocarcinoma, sarcoma, carcinoid, thyroid carcinoma, and melanoma.^19,20 Since the malignant transformation is a rarity and the malignant and benign forms represent a similar appearance, it is challenging to make a preoperative diagnosis. Rim et al.²¹ reported that the malignant transformation of dermoid cyst occurred at an average age of 56.8 years, and 63% of the cases were older than 40 years at the time of diagnosis.

The symptoms at presentation are variable in both benign and malignant tumors with some patients presenting with acute abdominal pain and mass effects whereas others with constitutional symptoms such as fatigue, anorexia/weight loss and urinary symptoms.²² Even though it is a neoplasm consisting of thyroid tissue, only 8% of patients with struma ovarii present with clinical hyperthyroidism.²³ Therefore, there are difficulties in the clinical diagnosis because of the absence of uniform diagnostic criteria due to the rarity of the disease. Various routes of metastasis described are as direct spread to the omentum and peritoneal cavity, the contralateral ovary, regional lymphatics to pelvic and para-aortic lymph nodes, and hematologic dissemination to the bone, lung, liver, and brain.^11,24

Devaney et al.²⁵ have advocated that the same guidelines should be followed for pathological diagnosis of malignant struma ovarii as those for thyroid carcinomas. Metastasis is rare in patients with malignant struma ovarii (5%).²⁵

There is controversy regarding the optimum treatment of malignant struma ovarii. The treatment alternatives include are radical surgery with or without thyroidectomy followed by adjuvant therapy that can be in form of external radiotherapy, chemotherapy, or thyroid suppression.²⁶ Various studies suggest that malignant struma ovarii should be treated with combination surgery including total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node sampling and thyroidectomy followed by Iodine-131 (I-131) therapy. Thyroidectomy is a part of radical surgery for two reasons: first to exclude the possibility of primary thyroid carcinoma and second, we can recognize the metastasis, recurrence, and residual tissue after thyroidectomy with total body scanning with I-131 and serum thyroglobulin levels. Serum thyroglobulin is used as a tumor marker for follow-up in these malignant cases. As there have been only a few reported malignant cases, there is no consistent data on the protocol of management of such cases. For the patients desiring fertility, treatment might be challenging. As proposed by Dardik et al.²³ fertility-sparing surgery should be performed first followed by definitive surgery after the completion of childbearing.

The reported case was also advised for surgical staging and thyroidectomy followed by I-131 therapy, but the patient agreed to surgical staging but refused for thyroidectomy. The survival rates of 12–180 months have been reported in the literature in patients of malignant struma ovarii treated without thyroidectomy.²⁷ As with our case we are unable to determine the metastasis, the residual tissue, or recurrence without thyroidectomy, we think that thyroidectomy should be a part of treatment for better follow-up and prognosis.

Yücesoy et al.²⁸ have published a similar case report in which following staging laparotomy, the patient refused thyroidectomy, and follow-up was done with serum thyroglobulin levels. Till her follow-up for 18 months, her thyroid profile was normal and the patient was healthy.

CONCLUSION

Struma ovarii is a monodermal variant of ovarian teratoma, defined by the presence of >50% thyroid tissue that generally occurs in women between the ages of 40 and 60 and usually presents as a unilateral adnexal mass. In view of controversy regarding the management and follow-up of this rare entity, more data and reporting of such type of cases is required for establishing the optimum management protocol. It is also necessary for the gynecologist to be aware of these rare conditions to avoid unnecessary delay in management.

REFERENCES

1. Berek JS, Hacker NF. Practical gynecologic oncology, 3rd edition. Philadelphia: Lippincott Williams & Wilkins; 2003. pp. 3–38.

2. Caruso PA, Marsh MR, Minkowitz S, et al. An intense clinicopathologic study of 305 teratomas of the ovary. Cancer 1971;27(2):343–348. DOI: 10.1002/1097-0142(197102)27:2<343::aid-cncr2820270215>3.0.co;2-b.

3. Hackethal A, Brueggmann D, Bohlmann MK, et al. Squamous cell carcinoma in mature cystic teratoma of the ovary: Systematic review and analysis of published data. Lancet Oncol 2009;10(5):446. DOI: https://doi.org/10.1016/S1470-2045(08)70306-1.

4. Koonings PP, Campbell K, Mishell DR, et al. Relative frequency of primary ovarian neoplasms: A 10-year review. Obstet Gynecol 1989;74 (6):921–926. PMID: 2685680.

5. Whitecar MP, Turner S, Higby MK. Adnexal masses in pregnancy: A review of 130 cases undergoing surgical management. Am J Obstet Gynecol 1999;181(1):19–24. DOI: 10.1016/s0002-9378(99)70429-1.

6. Blackwell WJ, Dockerty MB, Mason JC, et al. Dermoid cysts of the ovary: Their clinical and pathological significance. Am J Obstet Gynecol 1946;51:151–172. DOI: 10.1016/s0002-9378(16)39889-1

7. Talerman A. Germ cell tumors of the ovary. In: Kurman RJ (Ed). Blaustein’s Pathology of the Female Genital Tract. 4th edition. New York: Springer-Verlag; 1994. pp. 849–914.

8. Matz MH. Benign cystic teratomas of the ovary. Obstet Gynecol Surv 1961;16:591–605.

9. Serov SF, Scully RE, Sobin LH. Histological typing of ovarian tumors. International Histological Classification of Tumors. No. 9. Geneva: World Health Organization; 1973.

10. Kabukcuoglu F, Baksu A, Yilmaz B, et al. Malignant struma ovarii. Pathol Oncol Res 2002;8:145–147.

11. Rosenblum NG, LiVolsi VA, Edmonds PR, et al. Malignant struma ovarii. Gynecol Oncol 1989;32 (2):224–227. DOI: 10.1016/s0090-8258(89)80037-x.

12. Volpi E, Ferrero A, Nasi PG, et al. Malignant struma ovarii: A case report of laparoscopic management. Gynecol Oncol 2003;90(1):191–194. DOI: 10.1016/s0090-8258(03)00142-2.

13. Yoo SC, Chang KH, Lyu MO, et al. Clinical characteristics of struma ovarii. J Gynecol Oncol 2008;19(2):135–138. DOI: 10.3802/jgo.2008.19.2.135.

14. Marti JL, Clark VE, Harper H, et al. Optimal surgical management of well-differentiated thyroid cancer arising in struma ovarii: A series of 4 patients and a review of 53 reported cases. Thyroid 2012;22(4):400–406. DOI: 10.1089/thy.2011.0162.

15. Peterson WF, Prevost EC, Edmunds FT, et al. Benign cystic teratomas of the ovary: A clinico-statistical study of 1007 cases with a review of the literature. Am J Obstet Gynecol 1955;70(2):368–382. DOI: 10.1016/s0002-9378(16)37681-5.

16. Talerman A. Germ cell tumors of the ovary. In: Kurman RJ (Ed). Blaustein’s Pathology of the Female Genital Tract, 3rd edition. New York: Springer Verlag; 2001. pp. 967–1033.

17. Yamashita Y, Hatanaka Y, Takahashi M, et al. Struma ovarii: MR appearances. Abdom Imaging 1997;22(1):100–102. DOI: 10.1007/s002619900150.

18. Ayhan A, Yanik F, Tuncer R, et al. Struma ovarii. Int J Gynaecol Obstet 1993;42:143–146. DOI: https://doi.org/10.1016/0020-7292(93)90628-A.

19. Hatanaka Y, Yamashita Y, Torashima M, et al. MR appearance of fat distribution in ovarian teratoma: Pathologic correlation. Nippon Igaku Hoshasen Gakkai Zasshi 1996;56(7):477–481. PMID: 8692663.

20. Kawakami S, Togashi K, Egawa H. Solid mature teratoma of the ovary: Appearances at MR imaging. Comput Med Imaging Graph 1994;18(3):203–207. DOI: 10.1016/0895-6111(94)90030-2.

21. Rim SY, Kim SM, Choi HS. Struma ovarii showing clinical characteristics of ovarian malignancy. Int J Gynaecol Cancer 2005;15(6):1156–1159. DOI: 10.1111/j.1525-1438.2005.00328.x.

22. Comerci Jr, Licciardi F, Bergh PA, et al. Mature cystic teratoma: A clinicopathologic evaluation of 517 cases and review of the literature. Obstet Gynecol 1994;84(1):22–28. PMID: 8008317.

23. Dardik RB, Dardik M, Westra W, et al. Malignant struma ovarii; Two case reports and review of the literature. Gynecol Oncol 1999;73(3):447–451. DOI: 10.1006/gyno.1999.5355.

24. Chan SW, Farrell KE. Metastatic thyroid carcinoma in the presence of struma ovarii. Med J Aust 2001;175(7):373–374. DOI: 10.5694/j.1326-5377.2001.tb143623.x.

25. Devaney K, Snyder R, Norris HJ, et al. Proliferative and histologically malignant struma ovarii: A clinicopathologic study of 54 cases. Int J Gynecol Pathol 1993;12(4):333–343. DOI: 10.1097/00004347-199310000-00008.

26. Makani S, Kim W, Gaba AR. Struma ovarii with a focus of papillary thyroid cancer: A case report and review of the literature. Gynecol Oncol 2004;94(3):835–839. DOI: 10.1016/j.ygyno.2004.06.003.

27. DeSimone CP, Lele SM, Modesitt SC. Malignant struma ovarii: A case report and analysis of cases reported in the literature with focus on survival and I131 therapy. Gynecol Oncol 2003;89(3):543–548. DOI: 10.1016/s0090-8258(03)00141-0.

28. Yücesoy G, Cakiroglu Y, Muezzinoglu B, et al. Malignant struma ovarii: A case report. J Korean Med Sci 2010;25(2):327–329. DOI: https://doi.org/10.3346/jkms.2010.25.2.327.