Malignant struma ovarii: The west of Scotland ... - Wiley Online Library

Journal of Medical Imaging and Radiation Oncology 56 (2012) 478–482 bs_bs_banner

RADIATION O N C O LO GY —O R I G I N A L A RTICLE

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Malignant struma ovarii: The west of Scotland experience and review of literature with focus on postoperative management Raj K Shrimali, Ghazia Shaikh and Nick S Reed Department of Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK

RK Shrimali MBBS, MRCP(UK), FRCR; G Shaikh MBBS, MRCP(UK), FRCR; NS Reed MBBS, MRCP(UK), FRCR, FRCP(Glas). Correspondence Dr Raj K Shrimali, Consultant in Clinical Oncology, Aberdeen Royal Infirmary, Foresterhill Road, Aberdeen AB25 2ZN, UK. Email: [email protected] Conflict of interest: None. Submitted 24 September 2011; accepted 21 December 2011. doi:10.1111/j.1754-9485.2012.02394.x

Abstract Introduction: Malignant struma ovarii is an extremely rare ovarian tumour containing malignant thyroid carcinoma within differentiated thyroid tissue, as the predominant tissue type. Surgery for suspected ovarian tumour and incidental pathological diagnosis is the most common presentation. Evidence supporting any particular approach to the clinical management of this condition is limited, mainly consisting of case reports, small series or pathological case series. There is no randomised evidence for postoperative management in view of the rarity of this condition. The opinion is divided between conservative management versus total thyroidectomy and radio-iodine ablation. Methods: We carried out a retrospective review of our series with focus on postoperative management of this rare condition. A review of existing literature was also carried out. Results: Six patients with a median age of 52 years presented with various symptoms of abdominal pain, pressure or menstrual problems. After the initial gynaecological resection and specialised pathology review, they were subsequently treated with total thyroidectomy and administration of radioactive iodine. All of these six patients are in remission at a median follow up of 60 months. Conclusion: We favour aggressive postoperative management with total thyroidectomy and radioactive iodine, and long-term follow up of these patients. Key words: ovary; radio-iodine; struma ovarii; thyroglobulin; thyroid cancer.

Introduction Malignant struma ovarii is an extremely rare germ cell tumour of the ovary characterised by the presence of malignant thyroid carcinoma within differentiated thyroid tissue, as the predominant tissue type, in an ovarian dermoid cyst. Surgery for suspected ovarian tumour and incidental pathological diagnosis is the most common presentation. Usually diagnosed pathologically after pelvic surgery, the opinion on postoperative management is divided. There are no internationally agreed guidelines nor is there any randomised evidence for any particular approach in view of the rarity of this condition. The published literature is mainly of case reports or small series together with expert pathology reviews. The opinion is divided between conservative management versus total thyroidectomy and radio-iodine ablation.

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Long-term follow up is recommended with clinical and biochemical monitoring with thyroglobulin levels and thyroid function test to detect residual or recurrent disease. We present a retrospective review of our series of six patients with malignant struma ovarii, who were treated in the west of Scotland in the last 7 years. Relevant literature with particular focus on postoperative management has been reviewed.

Methods Six patients with malignant struma ovarii were treated at the Beatson Cancer Centre, over a 6-year period between 2004 and 2009. The medical case records of the six identified patients were analysed and a retrospective review was carried out in late 2010, in conjunction with

© 2012 The Authors Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists

Malignant struma ovarii

roidectomy and radioactive iodine ablation (4000 MBq of iodine-131). The subsequent three patients progressed directly to total thyroidectomy and radioactive iodine ablation after the initial gynaecological procedure (Table 1). The thyroidectomy specimens were clear of malignancy in all of our patients. None of the patients reported any side effects, acute or delayed, from radioactive iodine therapy. The follow-up period after post-thyroidectomy radioactive iodine ablation varies from 17 to 75 months with a median follow up of 60 months. They are currently on long-term thyroid replacement and thyroid stimulating hormone (TSH) suppression with thyroxine and are reviewed once every 6 months for the first 2 years and annually thereafter. Thyroglobulin levels and thyroid function tests are performed at every visit. All our patients are alive and remain in remission clinically, biochemically and radiologically.

a review of the literature. The demographics, presenting symptoms, initial gynaecological surgery, histology, postoperative treatment plan and follow up were studied. Benign struma patients are not included in this study.

Results Age of our six patients at presentation ranged from 35 to 59 years (median: 52 years). Three of the patients presented with menstrual problems of postmenopausal bleeding, irregularity or cyclical pelvic pain. The remaining three presented pressure effects from ovarian cysts leading to dyspepsia, renal infection or abdominal distension (Table 1). Patient 1 had an atypical presentation and unusual sequence of events and has been discussed separately prior to the discussion. All our patients underwent resection of the primary tumour. Two out of six patients underwent conservative resection such as unilateral oophorectomy or salpingooophorectomy (SO). Of the remaining four patients who underwent total abdominal hysterectomy (TAH) and bilateral SO (BSO), two patients also received omental biopsy or omentectomy and washings (Table 1). Three patients were found to have a histological diagnosis of follicular carcinoma and the remaining three had papillary thyroid carcinoma in their ovarian struma (Table 1). All of our cases underwent specialised pathology review. After the initial gynaecological surgery, the first three patients received a diagnostic whole body radionuclide scintigraphy with radioactive iodine, which did not show any abnormal uptake. This was followed by total thy-

Patient 1 (atypical presentation and unusual sequence of events) The first patient in our series presented in February 2004 with postmenopausal bleeding. She had previously undergone TAH and left SO for presumed benign ovarian teratoma in 1996. Biopsy from a small polyp at the vaginal vault was reported as showing malignant follicular thyroid tissue, consistent with malignant struma ovarii. Subsequent specialised pathological review of the previous surgical specimen and current biopsy confirmed struma ovarii in both present and previous samples.

Table 1. Presentation, initial surgery, postoperative management and follow up Case

1

Age

Year of presentation

52

2004

Presenting symptoms Menstrual symptoms

Initial surgery

Precise histology

Postoperative management

Follicular carcinoma

Follicular carcinoma

Normal Ra-I scan but raised thyroglobulin prior to total thyroidectomy and I-131 ablation Laparotomy and excision of vaginal vault mass Normal Ra-I scan prior to total thyroidectomy and I-131 ablation

Papillary carcinoma Follicular carcinoma

Normal Ra-I scan prior to total thyroidectomy and I-131 ablation Normal Ra-I scan after total thyroidectomy and I-131 ablation

Papillary carcinoma Left Papillary salpingo-oophorectomy carcinoma

Normal Ra-I scan after total thyroidectomy and I-131 ablation Normal Ra-I scan after total thyroidectomy and I-131 ablation

TAH and BSO in 1996 Recent biopsy of vaginal vault

2

59

2004

Ovarian cyst and renal infection

3

52

2005

4

53

2006

5

50

2006

6

35

2009

Menstrual symptoms Dyspepsia and supra-pubic mass Menstrual symptoms Abdominal distension

TAH, BSO, omentectomy, appendectomy and washings Unilateral oophorectomy TAH, BSO and omental biopsy TAH and BSO

I-131 treatment

Follow up

Nov-04

Remission

Apr-05

Remission†

Jun-05

Remission

Sep-06

Remission

Nov-06

Remission

Aug-09

Remission

†Subsequently underwent a complete resection for a gastric gastrointestinal stromal tumour (a second primary cancer) and currently on chemotherapy for a subsequent serous ovarian cancer (a third cancer). BSO, bilateral salpingo-oophorectomy; I-131, radioactive iodine; TAH, total abdominal hysterectomy. © 2012 The Authors Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists

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Although her whole body radioactive iodine scan was negative for the vaginal vault, her thyroglobulin level was raised at 294 mg/L (normal levels are less than 35 mg/L). After staging scans, she underwent laparotomy in July 2004, multiple tumour deposits were found at vaginal vault and remaining ovary which were all excised. Subsequently, she was treated with total thyroidectomy followed by radio-iodine ablation. Post-ablation iodine scan again did not show any abnormal uptake. She stays in remission on long-term thyroxine and thyroglobulin levels remain undetectable.

Discussion Struma ovarii is a specialised form of ovarian germ cell tumour. Mature ovarian teratoma comprises 0.2–1.3% of all ovarian tumours.1 Thyroid tissue has been found in 5–15% of all teratomas.2,3 Pathologically, if teratoma contains more than 50% of thyroid tissue, then it is classified as a struma ovarii.4 This should be distinguished from strumal carcinoid, which is usually defined as containing less than 50% thyroid tissue and may be considered as a monodermal teratoma. Five per cent of all germ cell tumours is struma ovarii.5 Struma can be benign or malignant. Various authors have quoted incidence of malignant struma varying from 0.1% to 5%.6,7 To be labelled as malignant struma ovarii, the histological features must be typical of a differentiated carcinoma. The differential diagnosis includes rare metastatic thyroid carcinomas. A recent paper by Roth and Talerman nicely discusses the challenges of diagnosing struma ovarii.8 The age of presentation varies from 21 to 77 years with mean age of 42 years.6,7 In our series, five out of six patients were in their 50s at initial presentation (Table 1). The most common presentation is a pelvic mass and related symptoms.6,7 In 94% cases, the adnexal mass is unilateral, commonly on the left side.1,9 Sometimes there is incidental finding of ovarian mass on imaging which prompts further investigations. Ascites is a relatively rare presentation reported to occur in 17% of cases by DeSimone and colleagues.7 Ascitic fluid rarely contains malignant cells.10 Pseudo-Meig’s syndrome has also been reported in benign and malignant struma ovarii.9–12 Meigs’ syndrome is well described in the literature as benign and solid ovarian tumours accompanied by ascites and hydrothorax, on condition that removal of this benign tumour reverses the other signs.13 When other conditions of the ovary are associated with ascites and hydrothorax, the term ‘pseudo-Meigs’ syndrome’ is used.14 Hyperthyroidism due to thyroxine secreting ovarian tumours may be a presenting feature in 5–8% of patients.6,9 Thyroglobulin and thyroid hormone levels have been reported to return to normal within a few weeks of definitive surgery in a thyrotoxic struma

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patient.15 ‘Non-malignant’ (or proliferative) struma ovarii (as discussed below) may also present with features of thyrotoxocosis. A vast majority of cases get diagnosed postoperatively based on histological findings discussed subsequently. There is little evidence to support whether CA 125 is useful or not in this condition. Some authors have reported that CA 125 measurement has little clinical value in malignant struma ovarii. It can be raised in both benign and malignant cases.16 In the published literature, the incidence of metastasis from malignant struma is quoted as 5–6%.17 However, Makani et al. have reported a higher incidence of 23%, mostly intra-abdominal.6 Metastasis can be intraperitoneal, haematogenous or lymphatic.7 The pathological differential diagnoses include strumal carcinoid and other papillary tumours and immunocytochemical staining for thyroglobulin may be helpful to confirm the presence of differentiated thyroid tissue.18 Devaney et al. have advocated the use of rigid pathological criteria, where the diagnosis of malignant struma ovarii is limited to lesions that show the full range of changes seen in primary thyroid carcinoma arising in the neck. They reviewed the histological features of 54 cases of struma ovarii and divided them into proliferative struma (41 cases) and malignant struma. Of the malignant struma (13 cases), 11 were papillary carcinoma and the remaining two were follicular. One papillary tumour was marked by a predominance of follicular areas showing a ‘mixed pattern’ (follicular variant of papillary carcinoma).4 There are rare reports of metastatic thyroid carcinomas to the ovary, so the thyroid should be checked by imaging (ultrasound or MRI) and fine needle aspiration and cytology.19 Papillary carcinomas must show ‘ground-glass’ overlapping nuclei and nuclear grooves lining papillary formations. Follicular carcinomas must display tumour cells arranged into microfollicles with invasion of the capsule and vascular spaces.4 Malignant ovarian struma of the follicular type is more difficult to diagnose than follicular thyroid carcinoma because a capsule is not typically present in ovarian samples.7,8 In our series, both papillary and follicular carcinomas were equally common. Proliferative struma was not reported to show any of these features and nuclear atypia and mitotic figures were rare. The risk of recurrence and metastases are very low, and conservative management may be appropriate with proliferative struma.4 None of our cases met these criteria. Because it is rare to recognise the diagnosis preoperatively, cases are usually managed as a suspicious ovarian tumour. The initial surgery will depend on whether the ovarian lesion is considered to have a low or high risk of malignancy using standard risk assessment criteria. For simple cysts, a conservative approach may be considered, whereas if the Risk of Malignancy Index is high, a standard ovarian cancer approach is advised.


Malignant struma ovarii

Therefore, the surgical procedure varies from full staging surgery for a suspicious ovarian cancer, which includes a TAH and BSO, omentectomy and peritoneal washings, to a more conservative surgery with unilateral oophorectomy to preserve fertility in a younger woman. However, if capsular invasion, vascular space invasion or gross metastases is observed on frozen section confirming malignant struma, full surgical staging as for ovarian cancer should be carried out. After conservative surgery in a younger patient, consideration should be given for delayed pelvic surgery once family is completed. These kinds of issues will be discussed at relevant tumour boards. Hatami et al. have suggested preoperative measurement of thyroglobulin along with other tumour markers in patients suspected of having a germ cell tumour,20 but this is of no proven value in differentiated thyroid cancers and is unlikely to be of value with struma ovarii. Volpi et al. published the first reported case of struma ovarii staged and surgically managed by laparoscopy, although numerous reports of laparoscopic surgical management of ovarian and pelvic tumours had been published prior to that.21 Distinction between a proliferative and malignant struma can be challenging.22 Consensus eludes the postoperative treatment of malignant struma ovarii because of its rarity. Adjuvant therapy reported in the literature includes total thyroidectomy, radioactive iodine ablation, thyroid suppression and external radiotherapy.6 The rationale for advocating a ‘near-total’ thyroidectomy is to remove all normal thyroid tissue so that the tumour marker thyroglobulin is more specific for malignancy. Thyroglobulin is not a reliable marker in the presence of residual thyroid tissue. It also allows radio-iodine ablation of the thyroid remnant as well as potential uptake in any metastases. After the diagnosis of malignant struma ovarii is established, the management is analogous to the treatment of primary differentiated thyroid carcinoma.7,23 All of our patients have been managed according to this philosophy (Table 1). Some series advocate routine total body radioactive iodine scan for evaluation of any postoperative residual disease.6 If residual malignant disease is identified, total thyroidectomy is recommended followed by radioactive iodine ablation and thyroid replacement thereafter.5,7,24,25 DeSimone et al. advocate thyroidectomy and radioiodine ablation as first line management for all patients with malignant struma ovarii. Thyroidectomy, despite its complications of hypocalcaemia, recurrent laryngeal nerve damage and long-term thyroid replacement, is the favoured treatment because of various reasons listed here; however, in expert hands, the risks of these complications will be less than 2–3%. Primarily, it confirms the diagnosis by excluding primary thyroid carcinoma as opposed to ovarian metastases. Secondly, it also allows radio-iodine ablation of the thyroid remnant as well as preferentially uptake in any residual struma or

metastases if present.7 Thirdly, the thyroglobulin levels are more reliable as tumour markers for follow up after total thyroidectomy and radioactive iodine ablation.23 In the series of 24 cases by DeSimone et al., all eight recurrences occurred in patients who did not receive thyroidectomy or radioactive iodine ablation. Of these, seven patients had an initial complete response to I-131.7 In our series, all patients with malignant struma were treated postoperatively with total thyroidectomy followed by radioactive I-131 ablation. They are all in remission from the struma ovarii, although one patient (patient 2) has been subsequently diagnosed with two further cancers. She underwent a complete resection for a gastric gastrointestinal stromal tumour (a second primary cancer) and is currently on chemotherapy for a subsequent serous ovarian cancer (a third cancer). Regular follow up is carried out with thyroglobulin level and thyroid function tests. Residual and recurrent malignant struma ovarii respond well to radioactive iodine ablation.7,26 Thyroglobulin is useful as tumour marker for detection of recurrences after thyroidectomy, I-131 ablation and thyroid suppression10,26,27. Any increase in thyroglobulin should prompt a follow-up total body I-131 scan to look for recurrence.6,10,25,27 Radioactive iodine ablation can be repeated for treatment of recurrent struma ovarii. Human recombinant TSH has been used to achieve concentration of I-131 in foci of metastatic struma ovarii for cytotoxic effect.5 External beam radiotherapy may be useful for palliation of extensive metastasis or non-iodine avid disease. Long-term follow up with serial thyroglobulin levels to detect recurrence and thyroid function tests to ensure adequate suppression of TSH is appropriate. Radioactive iodine scan should be used when recurrence is suspected on the basis of rising thyroglobulin levels.6 Positron emission tomography/CT scans are useful for detecting recurrence in patients who have non-iodine avid disease in thyroid cancer and thus it may be assumed that they have a similar role in malignant struma.28 This series (of six cases) with focus on postoperative management of this condition and review of existing literature is one of the largest recent clinical series. We favour aggressive postoperative management and long-term follow up of these patients.

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