Lethal, Malignant, Metastatic Struma Ovarii

Pierre-Yves Marcy,1 Juliette Thariat,2 Danielle Benisvy,3 and Pierre Azuar4

Background: Struma ovarii (SO) is extremely rare, with less than 200 reported cases in the medical literature. SOis defined by the presence of an ovarian tumor containing thyroid tissue as the predominant cell type. Malignanttransformation is rare and lethal cases of SO are even rarer. We report on a patient presenting with left ovariancystic SO and lethal outcome.Summary: A 45-year-old woman was diagnosed with a follicular variant of papillary carcinoma on lapa-rotomy and left salpingo-oophorectomy. She had persistently elevated serum thyroglobulin following totalthyroidectomyþ radioiodine and second-look surgery. Imaging scan analysis showed pelvic tumor recur-rence and hypervascular liver metastases during follow-up as well as peritoneal carcinomatosis in thepelvis, right abdominal wall, and malignant ascites. The patient died from cachexia at 37 months afterdiagnosis.Conclusions: Such an aggressive malignant disease and lethal course of SO is rare. Total thyroidectomy ismandatory to exclude a primary thyroid neoplasm and for radioiodine therapy and follow-up. SO mayspread to contralateral ovary, pelvic nodes, peritoneum, liver, lungs, and bones through hematogeneousspread, which is different from the dissemination pattern of papillary thyroid carcinomas. Imaging high-lights the mixed behavior of this ovarian tumor.

Introduction

Approximately 15% of ovarian teratomas have asmall nonsignificant focus of thyroid tissue. Between

0.8% and 3% of ovarian teratomas contain functional thyroidtissue or are mostly made of thyroid tissue. They are thusclassified as struma ovarii (SO). SO is rare, malignant trans-formation is extremely rare, and lethal cases of SO are ex-ceptional. In this report, we present a patient with a very rarecase of lethal, malignant SO.

Patient

A 45-year-old woman presented with abdominal pain,anorexia, and recent weight loss of 14% of her usual weight(usual body–mass index of 24.1). The patient had a history oflaparotomy and left salpingo-oophorectomy for an 11-cmovarian cyst (Surgery 1) at 11 months earlier. Ca-125 level waswithin normal limits. Histology had revealed a follicularvariant of papillary carcinoma in a left-sided SO. Second-lookcontralateral salpingo-oophorectomy, hysterectomy, omen-tectomy, retroperitoneal lymph node excision, and peritonealcytology (Surgery 2) were negative for malignancy. Sub-

sequent total thyroidectomy was delayed because the patienthad been refusing thyroidectomy for 1 year. Histology of thethyroid ruled out primary malignancy. Postthyroidectomyserum thyroglobulin (Tg) was elevated (407 mg/mL; thyroidstimulating hormone (TSH)<0.03 mUI/L) but the patient hadnot regularly taken her suppressive hormonal therapy. Atcase presentation, computed tomography (CT) and magneticresonance imaging (MRI) scan analysis showed a hypervas-cular and necrotic hepatic nodule (VI–VII liver segments) anda left pelvic mass. Subsequent laparoscopy (Surgery 3) re-vealed multiple nodules of peritoneal carcinomatosis in thepelvis, right abdominal wall, and malignant ascites with bi-opsy-proven metastases of the liver and pelvis (Fig. 1); serumTg level was increased to 2,445 080 mg/ml. 131I whole-bodyscan (WBS) showed limited uptake in the neck and multifocaluptake in the abdomen (right liver) and pelvis. The WBS wasfollowed by radioiodine therapy (131I, 7.4 GBq/200 mCi) anda further WBS disclosed iodine avidity, disappearance of bonemetastases, and global stabilization of liver lesions. The pa-tient underwent four courses of chemotherapy (cisplatin,doxorubicin) and two other therapeutic radioactive 131I infu-sions over a period of 27 months (5.4 GBq/147 mCi and 6GBq/162 mCi). Serum Tg level doubled within 3 months at

Departments of 1Head and Neck Imaging, 2Radiation Therapy, and 3Nuclear Medicine, Antoine Lacassagne Cancer Research Center, Nice,France.

4Department of Oncology Surgery, Centre Hospitalier de Grasse, Chemin de Clavary, Grasse, France.

THYROIDVolume 20, Number 9, 2010ª Mary Ann Liebert, Inc.DOI: 10.1089/thy.2010.0022

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postchemotherapy control, CT/MRI showed tumor pro-gression, and WBS still showed iodine hyperavidity. Despitethe therapy, the patient developed locoregional diseaseprogression (Fig. 2) and lung, adrenal, and bone metastases.The patient died from cachexia (body–mass index of 15.9) at37 months after diagnosis.

Discussion

SO was first described by Von Kalden in 1895 (1). In aseries of 1390 ovarian tumors, 12% were identified asteratomas and only 0.4% as SO (1,2). SO most commonlyoccurs in the fifth and sixth decades of life. The histo-logical diagnosis relies on a monodermal ovarian tera-toma, which contains more than 50% of mature thyroidtissue with large follicles containing abundant colloid. Thediagnosis is often made incidentally on abdominal/pelvicultrasound or during surgery. Focal increased pelvic up-take on WBS or elevated serum Tg have been reportedduring follow-up of differentiated thyroid cancer (2,3).Occasionally, there are symptoms of hyperthyroidism.Five percent to 10% of SO become malignant, the onlyabsolute criterion for which is the presence of distantmetastasis. Malignant transformation may be associatedwith V-raf marine sarcoma viral oncogene homolog B1(BRAF) mutations (3). Malignant SO consists of follicularvariant of papillary thyroid carcinoma (54%), papillarythyroid carcinoma (21%), mixed follicular/papillary car-cinoma (12.5%), or follicular carcinoma (4). It can includeelements of mucinous cystadenocarcinoma, Brenner tu-mor, carcinoid, or melanoma. To establish the diagnosis,

one must rule out the following differential diagnoses:ovarian metastasis from a thyroid primary neoplasm,clear-cell adenocarcinoma, or tumor of oxyphilic appearanceof the ovary (5,6). In the present case, increased serum Tgconcentration, histology-proven peritoneal seeding, and ra-dioactive iodine uptake in the liver and peritoneum on WBSwere suggestive of the diagnosis (7). According to the litera-ture, 88 malignant SO cases have been reported so far; theoverall survival rate is 89% and 84%, respectively, at 10 and25 years (8–10). Most frequent clinical symptoms include anabdominal mass (78%) or acute pain (22%) (4). Aggressivedisease course is rare (5–7). Most tumors spread to the pelvicnodes, contralateral ovary, peritoneum, liver, lungs, andbones. Kim et al. recently described a case of peritoneal stru-mosis with favorable outcome (11). In contrast to their case,our patient did not respond well to radioactive iodine andhad a very short survival. According to Robboy et al., adhe-sions, peritoneal fluid (>1 L), and ovarian serosal rent mayexplain the poor prognosis (10). This is the fifth lethal casereported in the literature (8,9). The patient recurred shortlyafter surgery, suffered from peritoneal carcinomatosis subse-quent to anorexia, and died from cachexia (31% weight loss)at 37 months. Interestingly, CT and MRI scans disclosed thespecific behavior of this well-differentiated tumor with in-tense uptake of radioactive iodine in metastases. Malignantovarian tumors spread to the liver capsula and along theperitoneum folders, whereas hematogeneous spread (bones,lungs, adrenals) is typical of follicular thyroid cancer. At theend of her disease, she had a pelvic tumor, ascites, andpleural effusion, the so-called modified pseudo-Meigs syn-drome triad (12).

FIG. 1. (A, B) Computed tomography axial scans display hypervascular nodular metastases of the right liver capsula (A,without contrast medium; B, with contrast medium; arrows) and cystic metastasis (*) scalloping the capsula. (C, D) Cysticperitoneal carcinomatosis (*) and right iliac fossa malignant micronodules (arrows) are shown on axial T2 weighted MRI scan.

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On the basis of our experience with this patient and othersin the literature, we recommend that thyroidectomy be per-formed quickly after pelvic surgery (13) to optimally eradicatethyroid remnants in the neck and pelvis by WBS. In addition,the serum TSH level should be rigorously maintained in theundetectable to very low range; new medications, includingvascular endothelial growth factor inhibitors, should be in-vestigated. Finally, the prevalence of BRAF and V-Ha-rasHarvey rat sarcoma viral oncogene homolog (HRAS) muta-tions in SO and their relationship to the prognosis and clinicalcourse of SO should be investigated.

Acknowledgment

We thank Professor F. Bussiere for reviewing this article.

Disclosure Statement

All authors have nothing to disclose and claim that nocompeting financial interests exist.

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FIG. 2. (A) Coronal computed tomography abdominal pelvic scans showing images fitting with hyperfixations on whole-body scan scintigram (B, anterior view). Note multifocal uptake of the liver, pelvis, and the right flank responding to capsularmetastases and local pelvic tumor recurrence (arrows).

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Address correspondence to:Pierre-Yves Marcy, M.D.

Department of Head and Neck ImagingAntoine Lacassagne Cancer Research Center

33 Avenue Valombrose06189 Nice cedex 1

France

E-mail: pymarcy@hotmail.com;pierre-yves.marcy@nice.fnclcc.fr

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