Squamous cell carcinoma arising in a dermoid cyst of the ovary: a case series
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1 DOI: /j x Gynaecological oncology Squamous cell carcinoma arising in a dermoid cyst of the ovary: a case series JL Hurwitz, a A Fenton, a WG McCluggage, b S McKenna a a Department of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UK b Department of Pathology, Belfast City Hospital, Belfast, UK Correspondence: Dr JL Hurwitz, Northern Ireland Cancer Centre, Lisburn Road, Belfast BT9 7AB, UK. jlhurwitz@hotmail.com Accepted 24 June Objective Malignant transformation in a dermoid cyst of the ovary is a rare complication, occurring in only 1 2% of cases, with squamous cell carcinoma being the most common type. Preoperative diagnosis is difficult because of the lack of specific symptoms and signs to suggest malignancy. Because of the small numbers of women involved, our knowledge of this rare tumour type is limited. This study aims to further characterise the population of women affected, the disease itself and the most appropriate management strategy. Design We identified 14 women with this diagnosis between 1989 and This is a descriptive study, looking at the patient characteristics, mode of presentation and the role of tumour markers and radiological imaging in diagnosis. We also examined the stage and pathological features of the tumour at presentation and the subsequent course of the disease. We have also described our experiences using surgery, chemotherapy and radiotherapy in the management of these women. Results We found that these tumours present at an age older than that of mature teratomas and that there are no reliable diagnostic tools or prognostic indicators. The behaviour of these tumours is unpredictable, and the role of chemotherapy and radiotherapy remains unclear. We suggest that repeated surgical resection of disease at the time of relapse could give a very durable response in selected women. Keywords Carcinoma, dermoid, ovary, squamous. Please cite this paper as: Hurwitz J, Fenton A, McCluggage W, McKenna S. Squamous cell carcinoma arising in a dermoid cyst of the ovary: a case series. BJOG 2007;114: Introduction Dermoid cysts account for approximately 20% of all ovarian tumours. 1 They occur more commonly in premenopausal women and are usually unilateral. Oophorectomy is the operative procedure of choice and is usually curative. Malignant transformation of the mature elements within the dermoid cyst is a rare complication, occurring in only 1 2% of cases, with squamous cell carcinoma being the most common type (making up to 80 90%), followed by adenocarcinoma. 2,3 Historically, these tumours have been diagnosed postoperatively, as preoperative features predicting the diagnosis are not well described. Due to its rarity, our knowledge about this tumour type is limited and currently based mostly on case reports. This study aims to further characterise the population of women affected by this disease, the disease itself and the most appropriate course of management. Cases We identified 14 women diagnosed with squamous cell carcinoma arising in a dermoid cyst of the ovary between 1989 and All the pathology diagnoses were confirmed in our pathology department, and a retrospective review of the patients case notes was carried out. In two women, pathology information only was available, and these have not been included in the study. One woman was lost to follow up 5 years after diagnosis (but was still alive and disease-free at this point). Patient characteristics The characteristics of the patients are outlined in Table 1. The age range at diagnosis was years, with a mean of 48 years. Three women presented with acute abdominal symptoms requiring emergency surgery. Eight women had more chronic symptoms, including generalised abdominal pain, urinary symptoms and anorexia/weight loss. There was no particular associated past gynaecological, medical or family histories. CA125 was normal in seven women, high in two women and not documented in three women. No other tumour markers was consistently checked. Eight women had documented evidence of preoperative imaging; four had ultrasound only, three had computed tomography (CT) and one had magnetic resonance imaging (MRI ). A diagnosis of malignancy within a dermoid cyst was ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology 1283
2 Hurwitz et al. Table 1. Summary of patient and disease characteristics Patient Year of diagnosis Age at diagnosis (years) Presenting symptoms CA125 Preoperative imaging Stage at diagnosis Grade/ differentiation Time to elapse Survival to date nd nd nd Ic Poor 2 years D 5 years Chronic Normal Ultrasound Incomplete* Poor n/a A 5 years Acute Normal Ultrasound IIb Poor,6 months D 8 months Chronic Normal Ultrasound III Poor,6 months R/A 4.5 years Chronic nd nd Ia Poor n/a A 3 years Chronic Normal CT Ic Poor n/a A 3 years Acute Normal Ultrasound Incomplete* Moderate,6 months D 9 months Acute nd Ultrasound Incomplete* Moderate n/a A 2.5 years Chronic Normal CT Ic Moderate n/a A 2 years Chronic 500 CT IIb Poor 3 months D 10 months Chronic Normal CT Ia Well n/a A 9 months Chronic 40 MRI III Poor n/a A 2 months A, Alive; D, Died; n/a, not applicable; nd, not documented; R, Relapsed. *Unilateral oophorectomy predicted only in two women, including our most recently diagnosed woman who had a MRI (Figure 1). Disease characteristics The characteristics of the tumours are outlined in Table 1. We then looked more closely at the actual pathological characteristics at presentation. There appeared to be a tendency to present at a lower stage than epithelial ovarian cancer. Three women had only unilateral oophorectomy and therefore were incompletely staged. Of the nine women who had staging surgery, there were five with stage I disease, two with stage II and two with stage III. Figure 1. MRI pelvis of case 12 showing mass arising from left ovary. This contains fat and abnormal cellular material, some of which projects anteriorly and is stuck to the sigmoid colon with loss of the plane of cleavage, suggesting malignancy. In terms of the pathological appearance of the tumours, there was a wide variation. For example, in case 11, there was only a 1-mm focus of invasive carcinoma adjacent to an area of dysplasia, whereas case 6 had a 3-cm tumour area perforating the ovarian capsule. The size of the overall tumour ranged between 5 and 15 cm. The mean was 9.6 cm. All the squamous tumours were unilateral. Figure 2 shows the typical histological appearance of this tumour. Treatment All our women had surgery as their initial management. Three women had unilateral oophorectomy only, all of whom were at the age of 35 years or younger. All the other nine women had total abdominal hysterectomy and bilateral salpingooophorectomy (TAH-BSO) as their initial surgery. One of the women had adjuvant treatment case 3 had two cycles of carboplatin chemotherapy postoperatively. Treatment was discontinued due to toxicity, but the woman relapsed within 3 months suggesting little benefit from chemotherapy. In terms of management of relapsed and metastatic disease, chemotherapy, radiotherapy and surgery have all been used. Case 1 had a small bowel resection and colostomy formation with complete debulking for recurrent abdominal disease 2 years after her original surgery. She relapsed 3 years later with pelvic disease. Pelvic radiotherapy was commenced, but she died during treatment. Case 4 had TAH-BSO with complete debulking for stage III disease initially. She developed peritoneal relapse 3 months later and received six cycles of carboplatin AUC 5/paclitaxel 175 mg/m 2 q 3 weeks disease was unassessable at time of chemotherapy but progressed again less than 6 months later. At this point, she received 16 cycles of paclitaxel 80 mg/m 2 with stable disease at the end of treatment but progressed 1284 ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology
3 Squamous cell carcinoma in a dermoid cyst of the ovary Figure 2. Dysplastic squamous epithelium, squamous carcinoma arising from dysplasia and invasive squamous carcinoma. again within 2 months of completion. She then had further surgery with complete debulking for recurrent mesenteric disease and has remained well with no evidence of recurrent disease for the 2.5 years since then. Case 7 relapsed 3 months after her initial surgery, and at this point, she had a sigmoid colectomy with incomplete debulking. This was followed for three successive lines of chemotherapy (carboplatin AUC 5 /5FU 1000 mg/m 2 d1-5 q 3 weekly, paclitaxel 175 mg/m 2 /carboplatin AUC 5 q 3 weekly and paclitaxel 80 mg/m 2 weekly) but had progressive disease after two to three cycles of all these and died 9 months after diagnosis. Case 10 relapsed 3 months after diagnosis with a large pelvic mass invading and eroding into the sacrum (Figure 3). She received radical pelvic radiotherapy at this time, and there appeared to be some initial symptomatic improvement. Her disease progressed again after 2 months, however, causing very difficult pain management issues due to sacral nerve root involvement, and she died 10 months after diagnosis. She was not considered fit for chemotherapy. Figure 3. CT showing large pelvic tumour with erosion into the sacrum. Overall, one woman was lost to follow up after 5 years but was alive and free of disease at this point. Of the 11 remaining women, 7 are alive and disease-free (follow up ranges from 2 months to 3 years). Two women are alive with recurrent disease, and three women are deceased (range from 8 months to 5 years). Discussion This case series is a moderately sized group compared with previous publications. Current opinion is that the women s age at presentation with malignant transformation in a dermoid cyst is older than those with benign disease and is more common in postmenopausal women. 1,4,5 The average age at presentation in our series was 48 years, which would be in keeping with these previous reports. There did not appear to be a correlation between age and prognosis in our women. We suggest that age is not necessarily a prognostic indicator but may be useful in terms of raising suspicion of malignant transformation when an older woman presents with what appears to be a benign dermoid cyst. Are tumour markers useful in terms of preoperative diagnosis? In our series, CA125 was only documented as high in two of our women and as normal in seven women. This would imply a lack of usefulness as a diagnostic tool and would be in keeping with the current published data as suggesting that CA125 does not predict this diagnosis preoperatively. 4 We found, in keeping with most other published series, that preoperative imaging with ultrasound or CT was of little value in predicting this diagnosis. In the woman who had MRI prior to surgery, there were features which pointed to malignancy suggesting that more modern imaging techniques may be of greater value in the preoperative assessment of these women. There are case reports emerging in the literature, which would support this view. Dermoid cysts typically show high signal intensities on both T1- and T2-weighted MRI images and the presence of fat-fluid levels. Malignant transformation may be shown by the presence of solid ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology 1285
4 Hurwitz et al. or necrotic contrast-enhancing areas that may extend transmurally and show evidence of adherence to surrounding structures. 6,7 In terms of predicting likelihood of disease relapse, stage appeared to be the most useful prognostic marker. Generally, women with stage Ia disease have an excellent prognosis (remaining free of recurrence 2.5, 3 and 5 years after diagnosis in our series). The role of tumour grade in predicting prognosis is less certain, but there did appear to be a tendency for those with less well-differentiated tumours to do less well. There is no clear consensus on an optimal management strategy for these women. Most centres would advocate that initial treatment should be with surgery, and this was the case in all our women. TAH-BSO and omentectomy would be the most widely accepted approach, as this allows full staging of the disease. Optimal debulking if metastatic disease is present is also thought to improve survival in these cases, as it does for primary epithelial tumours. 1 Three of our women (who were aged 35 or younger) were initially treated with unilateral oophorectomy. Of these, one woman is now lost to follow up but was alive and disease-free at 5 years from diagnosis, one is disease-free at 2.5 years from diagnosis and the third died 9 months after diagnosis. The question as to whether fertility sparing surgery is appropriate for young women with disease localised to one ovary has never been definitively answered. However, given that this disease is generally unilateral, this would seem a reasonable option to at least discuss with women who wish to preserve fertility. The role of radiotherapy and chemotherapy in this disease remains unclear, and the authors vary in their opinion. In women deemed at high risk of disease relapse, postoperative radical pelvic radiotherapy may be considered. 3 The rational for this is that in patients who did relapse, pelvic disease was common and a particularly difficult problem to manage clinically. We observed little benefit of radiotherapy in the metastatic setting. In terms of chemotherapy, it would be fair to conclude from previous studies that chemotherapy is less effective in this disease than in primary epithelial ovarian tumours. 1 While some case series have reported some evidence of chemosensitivity, we have observed no definite benefit from chemotherapy in any of our women, either in the adjuvant or metastatic setting. It must be emphasised, however, that the series is small and the chemotherapy regimens used varied, and the possibility that chemotherapy may be of benefit in some women cannot be completely discounted. Also while most women in this series (in common with others reported 3,4 ) had regimens used to treat epithelial ovarian cancer, it is possible that regimens more commonly used in the treatment of squamous tumours such as cisplatin and 5-flurouracil may have demonstrated more convincing evidence of activity. Concurrent chemoradiation has also been advocated by several authors in a similar manner to that used for squamous cell carcinomas of the cervix, with varying results. 1,8 The value of secondary debulking surgery is clearly demonstrated in two women (case 1 and 4), where durable remissions have been obtained following relapse. This is an approach that has not previously been emphasised in the literature, but our experience would suggest that surgery should be considered as initial management in all women with relapsed disease. It is likely to be most useful in those with a reasonably long disease-free interval and single site of relapse. Conclusions This series of women confirms that these tumours present on average at an older age than mature teratomas. It is historically difficult to diagnose this disease preoperatively, as neither serum tumour markers nor imaging with ultrasound or CT reliably predicts the specific diagnosis. Modern imaging techniques, such as MRI, appear to be more useful however. We found that the behaviour and clinical course of the disease are unpredictable, and although there is no clear consensus on the optimal management of these women, we propose the following guidelines: Optimal initial surgical management is TAH-BSO and omentectomy. Unilateral oophorectomy may be considered in women wishing to preserve fertility. In women whose disease has been optimally debulked, adjuvant radical pelvic radiotherapy may be considered in those who are felt to be at high risk of relapse. The addition of concurrent chemotherapy with a platinum-based regimen could be considered. The value of chemotherapy and radiotherapy in the metastatic setting is unproven. Secondary debulking should be considered, as this appears to produce very durable remissions in a proportion of women. j References 1 Tseng CJ, Chou HH, Huang KG, Chang TC, Liang CC, Lai CH, et al. Squamous cell carcinoma arising in mature cystic teratoma of the ovary. Gynecol Oncol 1996;63: Powell JL, Stinson JA, Connor GP, Shiro BS, Mattison M. Squamous cell carcinoma arising in a dermoid cyst of the ovary. Gynecol Oncol 2003;89: Tangjitgamol S, Manusirivithaya S, Sheanakul C, Leelahakorn S, Thawaramara T, Jesadapatarakul S. Squamous cell carcinoma arising from dermoid cyst: case reports and review of literature. Int J Gynecol Cancer 2003;13: Kikkawa F, Ishikawa H, Tamakoshi K, Nawa A, Suganuma N, Tomoda Y. Squamous cell carcinoma arising from a mature cystic teratoma of the 1286 ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology
5 Squamous cell carcinoma in a dermoid cyst of the ovary ovary: a clinicopathologic analysis. Obstet and Gynecol 1997;89: Kikkawa F, Nawa A, Tamakoshi K, Ishikawa H, Kuzuya K, Suganuma N, et al. Diagnosis of squamous cell carcinoma arising from mature cystic teratoma of the ovary. Cancer 1998;62: Takemori M, Nishimura R. MRI findings of an ovarian dermoid cyst with malignant transformation. Magn Reson Med Sci 2003;2: Kido A, Togashi K, Konishi I, Kataoka ML, Koyama T, Ueda H, et al. Dermoid cysts of the ovary with malignant transformation: MR appearance. AJR Am J Roentgenol 1999;172: Dos Samos L, Mok E, Iasonos A, Park K, Soslow RA, Aghajanian C, et al. Squamous cell carcinoma arising in mature cystic teratoma of the ovary: a case series and review of the literature. Gynecol Oncol 2007;105: ª 2007 The Authors Journal compilation ª RCOG 2007 BJOG An International Journal of Obstetrics and Gynaecology 1287
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