Malignant Ovarian Germ Cell Tumours: Is there any clue for its diagnosis?

Transcription

1 Malignant Ovarian Germ Cell Tumours: Is there any clue for its diagnosis? Poster No.: C-0485 Congress: ECR 2014 Type: Educational Exhibit Authors: M. Horta, T. M. Cunha; Lisbon/PT Keywords: Cancer, Diagnostic procedure, Ultrasound, MR, CT, Genital / Reproductive system female DOI: /ecr2014/C-0485 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 49

2 Learning objectives - To analyse and understand the epidemiology and histogenesis of malignant germ cell tumours of the ovary. - To describe and illustrate the imaging findings, highlighting the diagnostic clues of these tumours. Page 2 of 49

3 Background Germ cell tumours arise from primordial germ cells and constitute approximately 30% of all ovarian neoplasms. Malignancy is extremely rare accounting only for 3% of all ovarian cancers in western countries, but for two-thirds of ovarian cancers that occur in the first two decades of life (table 1 and 2) [1-4]. Table 1 References: Adapted from "Quirk JT, Natarajan N. Ovarian cancer incidence in the United States, Gynecol Oncol May;97(2):519-23" Page 3 of 49

4 Table 2 References: Adapted from "Breen J, Denehy T, et al. Pediatric Ovarian Malignancies. Glob.libr. women's med (ISSN: ) 2008" This group of neoplasms includes dysgerminomas, yolk sac tumours, embryonal carcinomas, non-gestational choriocarcinomas, immature teratomas, somatic carcinomas associated with mature teratoma, monodermal carcinomas and mixed germ cell tumours (table 3) [5]. Page 4 of 49

5 Table 3 References: Adapted from "Breen J, Denehy T, et al. Pediatric Ovarian Malignancies. Glob.libr. women's med (ISSN: ) 2008" Knowledge of the embryology of the ovary is essential to understand malignant germ cell tumours (MGCT), since they recapitulate normal embryogenesis [4]. The histogenesis of the various subtypes of germ cell tumours is shown on table 4 [6,7]. Dysgerminomas are composed of cells that are similar to primordial germ cells, which had not acquired the potential for further differentiation [5,7]. Embryonal carcinoma is a germ cell tumour, composed of poorly differentiated totipotential cells that are capable of further differentiation. Differentiation can occur in a somatic/embryonal direction resulting in teratoma that consists of a combination of tissues from all blastodermic layers (ecto- meso- and endoderm). On the other hand, differentiation can take place in an extraembryonal direction (vitteline or trophoblastic) resulting in yolk sac tumour or choriocarcinoma respectively [5,7]. Germ cells that have gone off the path or stranded along the line of migration from the wall of the yolk sac and the gonadal ridge, may develop into germ cell tumours outside the gonads [5]. Page 5 of 49

6 Table 4 References: Adapted from " Teilum G. Tumours of Germinal Origin.UICC Monograph Series Volume 11, 1968, pp 58-73" There is a remarkably similarity between male and female malignant germ cell tumours. Ovarian MGCT are usually large (medium size 16 cm), and with exception of dysgerminomas, most of the tumours are unilateral [1]. The typical patient is a young woman who presents with a large solid adnexal mass and with abdominal pain and/or abdominal bulging. Acute pain may be due to torsion, rupture Page 6 of 49

7 or haemorrhage, although it can be caused by peritoneal stretching and pressure on adjacent organs [1]. Patients may also have vaginal bleeding or fever. Precocious puberty has been described associated with immature teratomas and nongestational choriocarcinoma [1,8]. Serum alpha-fetoprotein (AFP), human chorionic gonadotropin (hcg) and lactate dehydrogenase (LDH) are useful markers of these tumours and should be part of the diagnostic workup. Dysgerminomas Dysgerminomas are the female counterpart of seminomas. They are the most common MGCT of the ovary, representing 0,5-2% of all ovarian tumours. It is the most common germ cell tumour associated with pregnancy, accounting for 20-30% of ovarian tumours diagnosed in this period or in the immediate post-partum [1,4,9]. nd rd 75% occur in early reproductive years (2-3 decade) and 10% in pre-pubertal girls [10]. Presenting symptoms are usually due to a rapidly growing of the pelvic mass. Serum levels of LDH are consistently elevated in this kind of tumours. In rare cases, it can produce hcg and patients may present with endocrine estrogenic symptoms, but rarely androgenic [4]. If serum levels of AFP are elevated one should think that a combined component of a yolk sac tumour may be present. Two-thirds of dysgerminoma are confined to the ovaries at the time of diagnosis, and differing from the other MGCT, 15% are bilateral. Metastatic rout is done mainly through the lymphatic system and metastases can occur lately in the disease. The malignancy of pure dysgerminomas is relatively low grade with survival rates of 80% to 96% [1]. Advanced grade dysgerminomas have a survival rate of 65%[10]. Yolk Sac Tumour Yolk sac tumours are the second most common MGCT of the ovary in children [10]. They occur at a median age of 18 and are rare in middle-aged or older women [4]. Page 7 of 49

8 Yolk sac tumours are almost all unilateral and usually present as a rapidly growing pelvic mass causing abdominal pain and bulging. Approximately 10% of tumours may present with acute abdominal pain caused by torsion or rupture. Elevated serum AFP is present in the majority of patients (usually greater than 1000 ng/ ml). It can be used as a tumour marker monitoring patients during and after therapy and to detect tumour recurrence [4]. CA 125 and CEA levels are also elevated in 100% and 10% of yolk sac tumours respectively [4]. Before the development of VAC (vincristine, dactinomycin, cyclosphosphamide) the prognosis for patients with yolk sac tumour was poor, being almost uniformly fatal [1]. Currently survival rates vary according to the stage at diagnosis, approaching 80% for patients with stage I and 40% for patients with higher stage tumours [4]. Worst prognosis is associated with tumour stage of II or higher, residual tumour >2 cm after surgery and presence of more than 100ml of ascites [4,10,11]. Embryonal Carcinoma Embryonal carcinoma is an extremely rare ovarian tumour, and one of most aggressive MGCT. The patients are young with a median age of 15 years old and present with the previously described signs and symptoms of a large unilateral pelvic mass. Serum levels of hcg are consistently elevated and are responsible for hormonal manifestations such as isosexual pseudoprecocity and irregular bleeding. AFP can occasionally be elevated without the presence of yolk sac components. It is a highly malignant tumour and advanced stage disease represents 40% of cases [4]. Despite this fact, cisplatin combination chemotherapy has resulted in long term survivors [4]. Immature teratoma Immature teratomas are the third most common MGCT of the ovary [12-14]. They constitute 20% of germ cell tumours and 1% of ovarian malignancies [4]. They differ from cystic mature teratomas in that they are less common (<3% of all ovarian teratomas), have a malignant behaviour and histologically they Page 8 of 49

9 are composed of a various amount of mature and immature tissue forms of mesenchymal and epithelial origin, derived from the three germ cell layers [4,12,15,16]. Presence of any immature tissue leads to the diagnosis of immature teratoma [12]. They may be associated with mature cystic teratomas. According to a retrospective study of 350 cases of immature teratomas and 10 cases of mature teratomas with microscopic foci of immature tissue, 26% of immature teratomas contained grossly visible mature teratoma in the contralateral ovary, and 2,6% were preceded by ipsilateral mature teratoma that have been removed years previously [16,17]. Immature teratomas are typically unilateral, with bilateral involvement being less than 5% [10]. At presentation they are typically larger than mature cystic teratomas [16]. More frequently they present as an asymptomatic palpable unilateral mass, but symptoms related to the presence of a large pelvic mass can occur. Elevated serum levels of AFP may be present (33-65%), however levels are not as high as those encountered with yolk sac tumours, and rarely exceed 1000ng/ml [7,12,13]. HCG, neuron-specific enolase (NSE), CEA and CA125 are other markers that can be elevated [4]. Grading of immature teratomas (1-3) is based on the amount of cellular immaturity [1]. In metastatic disease, the histologic grade of metastatic disease is the most important factor in predicting prognosis [1]. Metastatic disease is usually confined to abdominal peritoneal cavity and must be differentiated from gliomatosis peritonei (presence of mature glial implants sometimes with ascites) that is present in 10% of cases and is not included in tumour staging. 10 year survival rates for immature teratomas are of 82% for grade 1, 62% for grade 2 and 30% for grade 3 [10]. Immature teratomas or peritoneal implants that underwent chemotherapy can undergo tissue maturation and take the appearance of a mature cystic teratoma. This is called "retroconversion phenomenon" [16,10]. Somatic carcinomas associated with mature teratoma (malignant degeneration of mature cystic teratomas). Malignant degeneration of mature cystic teratomas must be differentiated from the immature form of teratoma, applying only to malignancy arising "de novo" in a pre-existing benign mature cystic teratoma [16]. Malignant transformation occurs in approximately 1-2% of mature cystic teratomas [18]. Page 9 of 49

10 The most common type of malignant degeneration is squamous cell carcinoma, accounting for 80-83% of cases [16,18]. Differing from mature teratomas, malignant transformation occurs in post-menopausal th th women (6-7 decades of life) [16,18]. Clinically, malignant transformation cannot be promptly identified, although in two thirds of patients, invasion and metastases have occurred before the diagnosis [18]. The prognosis is poor. Monodermal Teratomas There are three types of monodermal teratomas: struma ovarii, ovarian carcinoid tumours and tumours with neural differentiation. They are rare germ cell tumour with a predominant benign clinical behaviour, but all three have potential for malignancy. Struma ovarii is composed of thyroid tissue that is the predominant or exclusive component [18,19]. It accounts for approximately 5% of all ovarian teratomas [19]. Thyroid malignancy arising from struma ovarii is reported in 5-10% of cases [19,20]. The term "malignant struma ovarii" should be avoided and should be replaced by the specific thyroid type carcinoma in struma ovarii. Papillary and follicular thyroid-types carcinomas are the most frequent malignancy occurring in this type of monodermal teratoma [21]. In many cases in which histological malignancy was documented, the clinical behaviour was benign and the majority of carcinomas did not spread beyond the ovary [21]. Most patients are 40 to 60 years of age, and besides a palpable pelvic mass, they can present with ascites, Meigs syndrome (hydrothorax), cervical thyroid enlargement and hyperthyroidism with high pelvic iodine uptake [4,19]. Malignancy usually occurs in lesions larger than 16-cm.Thyroid carcinoma arising in struma ovarii rarely metastasizes. Metastases occur first by peritoneal implants (strumosis) and afterward by haematogenous spread to bone, liver, brain and lungs [10,19]. Occasionally serum CA125 may be elevated [10,19]. Carcinoid tumours have a relatively benign clinical course and low malignant potential. Less than 5% are complicated by metastases and death [4]. Page 10 of 49

11 Primary carcinoid tumours are divided in insular, trabecular, strumal and mucinous types. The majority occurs combined with a mature cystic teratoma, but 15% may occur in its pure form. They mainly occur in post-menopausal women and represent less than 0,1% of all ovarian tumours. Most patients present with unspecific symptoms relating to an unilateral ovarian enlarging mass. The carcinoid syndrome (facial flushing, diarrhoea, bronchoconstriction, hypertension and oedema secondary to carcinoid heart disease) is uncommon [10,16]. Many rare monodermal teratomas with neuroectodermal differentiation have been described in the ovary. They include ovarian ependymomas, which behave in a benign fashion and are associated with good outcome, but they also include primitive neuroectodermal tumours and anaplastic tumours resembling glioblastoma multiforme, both of which have very poor prognosis [4]. These tumours occur at an average age of 23 years old and are commonly unilateral. Anaplastic neoplasms can be large an often spread beyond the ovaries at the time of diagnosis [4]. Non gestational choriocarcinoma Non gestational choriocarcinoma is a highly malignant neoplasm that represents less than 1% of ovarian tumours. It occurs in prepubertal girls and postmenopausal women, who usually present with symptoms relating to a large pelvic mass. Serum levels of hcg are usually elevated and are responsible for isosexual pseudoprecocity in prepubertal girls or menstrual abnormalities in older patients [4]. Occasionally haemoperitoneum signs due to tumour or metastases haemorrhage can occur, which combined with an elevated serum level of hcg can simulate an ectopic pregnancy. It can invade pelvic structures, spread into peritoneal cavity and metastasize via lymphatics and blood stream to lung and brain. Brain metastases occur in 20% of patients and are the main cause of death [10]. Mixed malignant germ cell tumours Mixed malignant germ cell tumours of the ovary are rare neoplasms containing two or more types of germ cell elements. Although any combination is possible, a dysgerminoma and a yolk sac tumour are constituents in the majority of cases. Immature teratomas are the third most common component. Mixed malignant germ cell tumours with an Page 11 of 49

12 embryonal carcinoma, non-gestational choriocarcinoma and polyembryoma components are less common [4]. Page 12 of 49

13 Images for this section: Table 1 Adapted from "Quirk JT, Natarajan N. Ovarian cancer incidence in the United States, Gynecol Oncol May;97(2):519-23" Page 13 of 49

14 Table 2 Adapted from "Breen J, Denehy T, et al. Pediatric Ovarian Malignancies. Glob.libr. women's med (ISSN: ) 2008" Page 14 of 49

15 Table 3 Adapted from "Breen J, Denehy T, et al. Pediatric Ovarian Malignancies. Glob.libr. women's med (ISSN: ) 2008" Page 15 of 49

16 Table 4 Adapted from " Teilum G. Tumours of Germinal Origin.UICC Monograph Series Volume 11, 1968, pp 58-73" Page 16 of 49

17 Findings and procedure details Dysgerminoma Dysgerminomas characteristically present as a multilobulated mass with prominent fibrovascular septa that can be demonstrated with colour/power Doppler and with contrast-enhanced CT and MR (fig. 1C) [10]. Necrotic and haemorrhagic areas present as anechoic or low-attenuation areas and demonstrate high-signal intensity on T2-weighted MR images (T2WI) and high-signal intensity on T1-weighted MR images (T1WI), respectively (figs. 1-3) [15]. Speckled calcifications may be seen. Fig. 1: Dysgerminoma of the left ovary in a 12-year-old girl. Transabdominal ultrasound (A and B) and colour Doppler ultrasound (C) images show a multilobulated solid adnexal mass with heterogeneous echogenicity and with prominent fibrovascular septa. A central necrotic component is seen on axial non-enhanced CT (D and E, arrows). Page 17 of 49

18 References: Ultrasound from Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. CT from Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 2: Dysgerminoma of the left ovary in a 12-year-old girl. Axial T2-weighted MR images (A-C). Axial T1-weighted MR image (D). DWI MR image (E). Gadoliniumenhanced fat-suppressed sagittal T1-weighted MR image (F). Sagittal T2-weighted MR image (G). The MR images of the same patient as previous show a multilobulated abdomino-pelvic mass with intermediate-signal intensity on T2WI (A-C and G) and low-signal intensity on T1WI (D). The mass show marked homogenous enhancement except the necrotic component which does not enhance (F). References: Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 18 of 49

19 Fig. 3: Bilateral dysgerminoma in a 18-year-old girl. Sagittal T2-weighted MR image (A and B). Sagittal T1-weighted MR image (C). Axial T2-weighted MR image (D). Axial contrast-enhanced CT image (E). Bilateral large, well-delineated solid lesion of the ovary. They display predominantly intermediate-signal intensity on T2WI (A, B and D) and low-signal intensity on T1WI (C). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 19 of 49

20 Fig. 4: Dysgerminoma of the right ovary in a 20-year-old woman. Transabdominal ultrasound (A), axial non-enhanced CT (B) and axial contrast-enhanced CT (C) images demonstrate a multilobulated solid mass. References: Dionisio T. Department of Radiology, Hospital de Braga, Braga/Portugal. Fig. 5: Sagittal T2-weighted MR image (A), coronal T2-weighted MR image (B), coronal T1-weighted MR image (C), axial T2-weighted MR image (D) and gadoliniumenhanced fat-suppressed axial T1-weighted MR image (E) of the same patient as previous show a large multilobulated solid mass of the right ovary that displays predominantly intermediate-signal intensity on the T2WI (A, B and D) and low-signal intensity on T1WI (C). References: Dionisio T. Department of Radiology, Hospital de Braga, Braga/Portugal. Yolk sac tumour (endodermal sinus tumour) Most yolk sac tumours are unilateral, large (medium diameter 15 cm) and complex pelvic masses (fig. 6). The tumour frequently extends into the abdomen and contains both cystic and solid areas, giving the tumour an honeycombed appearance on ultrasound, CT and MR (fig. 7) [22]. Page 20 of 49

21 Contrast enhanced CT and MR show strong enhancement due to the tumour hypervascularity and sometimes central necrosis (figs. 7 and 8) [10]. T1-weighted MR images usually show a predominantly hypointense solid tumour with occasional hyperintense foci representing haemorrhage. On T2WI the tumour demonstrates an heterogeneous high-signal intensity with areas of very high-signal intensity representing necrosis. Multiple signal voids structures may be present. Fat-saturated T1WI may demonstrate saturation of the cyst contents, suggesting the presence of a concurrent mature teratoma. Ascites (fig. 8), peritoneal implants, urinary obstruction and enlarged pelvic and paraaortic lymph nodes may be seen [10]. Fig. 6: Yolk sac tumour of the right ovary in a 21-year-old woman. Transabdominal ultrasound images (A and B) demonstrate a complex adnexal mass. References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 21 of 49

22 Fig. 7: Yolk sac tumour of the left ovary in a 13-year-old woman. Contrastenhanced CT scan (A and B) show a multilobulated pelvic mass that extends into the abdomen with both solid and cystic components, giving the tumour an honeycombed appearance. There is an avid irregular enhancement of the solid portions (blue arrow). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 8: Yolk sac tumour of the right ovary in a 25 year-old woman. Contrast-enhanced CT scan (A and B) show a lobulated adnexal mass with an avid enhancement of the solid areas (blue arrows) and with central necrosis (blue asterisk). Ascites is present. References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Embryonal Carcinoma Page 22 of 49

23 Embryonal carcinoma usually presents as a very large abdomino-pelvic mass, therefore transabdominal pelvic ultrasound is mandatory since it can be missed by transvaginal ultrasound alone (fig. 9A) [10]. They frequently manifest as a predominant solid mass with large anechoic, lowattenuation or low-signal intensity areas, representing necrosis (figs. 9B and 10B, red asterisks). T1 and T2 MR signal characteristics vary according to the extent of necrosis and haemorrhage. There is an avid enhancement of the solid component of the mass on contrast-enhanced CT and MR. Associated ascites, peritoneal implants, retroperitoneal lymphadenopathies and lung or liver metastases may be seen at the time of diagnosis [10]. Fig. 9: Embryonal carcinoma of the right ovary in a 11 year-old girl. Transabdominal pelvic ultrasound image (A). Contrast-enhanced CT image (B) shows a very large solid right adnexal containing low-attenuating areas indicative of necrosis or haemorrhage (red asterisks). Note the presence of peripheral calcifications (red arrow). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 23 of 49

24 Fig. 10: Embryonal carcinoma. Axial contrast-enhanced CT scan (A and B) demonstrates a large predominantly solid tumour with areas of necrosis/haemorrhage (red asterisk) and with speckled calcifications (red arrows). References: Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Immature teratoma Ultrasound appearance of immature teratoma is non-specific [16]. They frequently manifest as an heterogeneous predominantly solid adnexal mass with cystic components. Highly echogenic foci producing posterior acoustic shadowing accounting for calcifications may be seen (fig. 11, green arrow). Foci of fat may be difficult to appreciate on US image [10,16]. On contrast-enhanced MRI and CT a complex mass with enhancing solid areas and cystic/haemorrhagic components is usually present (figs. 12 and 13). At CT small foci of low-attenuation fat (fig. 12, arrowheads) and high-attenuation calcifications (fig. 12, green arrows) are diagnostic clues. Foci of fat typically have highsignal intensity on T1WI and T2WI and signal loss on the fat saturation sequence. Capsule penetration suggests the presence of an immature teratoma instead of a mature teratoma [27]. Ascites and peritoneal implants are seen in advanced stage disease [10]. Fig. 14 shows the "retroconversion phenomenon" of an immature teratoma and of its peritoneal implants. Page 24 of 49

25 Fig. 11: Immature teratoma of the right ovary in a 11 year-old-girl. Ultrasound transabdominal images (A and B) demonstrate a predominantly solid mass with cystic components. Note the presence of highly echogenic material producing posterior acoustic shadowing suggestive of intratumoral calcifications (green arrow). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 25 of 49

26 Fig. 12: Grade 2 immature teratoma of the right ovary in a 24 year-old girl. Axial contrast-enhanced CT scan (A and B), sagittal contrast-enhanced CT scan (C) and coronal contrast-enhanced CT scan (D) show an heterogeneous large mass of the right ovary, with enhancing solid areas/septa and cystic/haemorrhagic components. Areas of fat attenuation are seen (green arrowheads) as well as scattered calcifications (arrows). Photograph of the gross specimen (E). References: CT from Ramalho M. Department of Radiology, Hospital Garcia da Orta, Almada/Portugal. Gross specimen from Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 13: Grade 2 immature teratoma of the right ovary in a 24 year-old girl. Axial T1weighted MR image (A), axial T2-weighted MR image (B), coronal T2-weighted MR image (C), sagittal T2-weighted MR image (D) of the same patient as previous, show an heterogeneous large mass of the right ovary, with cystic components. Gadoliniumenhanced fat-suppressed axial T1 weighted MR image (E), confirms the presence of enhancing solid components and multiple septa. Photograph of a detail of the gross specimen (F). References: MR from Lourenço AR. Department of Radiology, Hospital Garcia da Orta, Almada/Portugal. Gross specimen from Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 26 of 49

27 Fig. 14: Grade 3 immature teratoma of the right ovary in a 12 year-old girl and its mature cystic teratoma appearance after chemotherapy (retroconversion phenomenon). Coronal contrast-enhanced CT scan (A), axial contrast-enhanced CT scan (B), coronal non-contrast-enhanced CT scan (C) and axial non-contrast-enhanced CT scan (D). An enormous heterogeneous mass containing calcifications and extensive foci of fat is shown (A and B). Figures C and D show the "retroconversion phenomenon" of the immature teratoma and of its peritoneal implants after chemotherapy taking the appearance of a mature cystic teratoma. References: Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 27 of 49

28 Somatic carcinomas associated with mature teratoma (malignant degeneration of mature cystic teratomas). Malignant degeneration of mature cystic teratomas should be suspected on MRI and CT if large irregularly marginated soft tissue components show transmural or intratumoral invasive growth (fig. 15E-G, orange arrows) [24,25]. Rokitansky's protuberance is a common site of malignancy and its contrast-enhancement may be helpful determining malignant transformation, although this is not necessarily truth (fig. 15A, B and E, orange asterisks) [18,24]. An obtuse angle between enhancing soft tissue component and the inner wall of the cyst is a common CT and MR finding (fig. 15F and G, green arrows) [24,26]. We present a case of a squamous cell carcinoma arising from a mature cystic teratoma of the right ovary in a 54 year-old-woman with the CT and MR signs previously described (fig. 15). Fig. 15: Squamous cell carcinoma arising from a mature cystic teratoma of the right ovary in a 54 year-old-woman. Contrast-enhanced CT scan (A-C), transabdominal Page 28 of 49

29 ultrasound (D), sagittal T2-weighted MR image (E), axial T1-weighted MR image (F), gadolinium fat-supressed axial T1-weighted MR image (G). Transabdominal ultrasound (D) demonstrates a huge cystic mass with thin septation and a round echogenic nodule that on axial contrast-material CT scan (A-C) shows a fat-fluid level (orange arrowhead) and a Rokitansky nodule (orange asterisks). The area that demonstrates fat attenuation shows high-signal intensity on T1WI (F) and demonstrates saturation on fat-supressed image (G) (orange arrowheads). An irregularly marginated soft tissue component is seen in the wall of the mature teratoma (orange arrows), that was proven to be a squamous cell carcinoma. It has low-signal intensity on both T1WI and T2WI (E and F), showing avid enhancing after administration of gadolinium (G, orange arrows). An obtuse angle between the enhanced soft tissue component and the inner wall is seen (F and G, green arrows). Photograph of a section of the gross specimen showing squamous cell carcinoma in the cystic wall (H). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Monodermal Teratomas Imaging findings of struma ovarii are unspecific [19,24]. US and CT usually demonstrate a complex-appearing mass containing solid and cystic areas (fig. 16A and B). Fat and calcifications may occasionally be identified within the tumour, mimicking a mature cystic teratoma [19]. However, avidly enhancing soft tissue component due to vascular thyroid tissue within the tumour is characteristic of this tumour [10]. On MR imaging the cystic areas may present variable signal intensity ("stained glass appearance") (fig. 16C-E). Some locules can show strong low signal intensity on T1WI and T2WI caused by gelatinous thyroid colloid material [10,19]. Page 29 of 49

30 Fig. 16: 71-year-old female patient with an ovarian lesion containing thyroid follicles and foci of papillary carcinoma, most probably representing a papillary carcinoma arising in a struma ovarii. Transabdominal ultrasound images (A and B), axial T1weighted MR image (C), fat-supressed axial T2-weighted MR image (D) and sagittal T2-weighted MR image (E) show a complex-appearing mass containing solid and cystic areas. The cystic areas show variable signal intensity ("stain glass appearance") and thick septations (C-E). Multiple signal voids are seen within the mass (D, arrow). Ascites is present (D and E, asterisks). References: Leite I, Cunha TM, Figueiredo JP, Félix A. Papillary carcinoma arising in struma ovarii versus ovarian metastasis from primary thyroid carcinoma: a case report and review of the literature. Radiology Case Oct; 7(10): Carcinoid tumours of the ovary can manifest as a solid enhancing nodule in the wall of a mature teratoma or as an enhancing solid mass [10]. Differentiation from other solid malignant tumours may be difficult, although necrosis is less common [10]. Non-gestational choriocarcinoma Choriocarcinomas are typically unilateral and appear as hypervascular solid tumours with cystic, haemorrhagic and necrotic central areas [10]. Ascites, peritoneal implants and metastases to lung and brain may be present at the time of diagnosis [10]. Page 30 of 49

31 Mixed malignant germ cell tumours Imaging characteristics of mixed malignant germ cell tumours of the ovary vary according to the germ cell constituents. We present two cases of a malignant mixed germ cell tumour comprising of both embryonal carcinoma and yolk sac tumour (figs. 17 and 18). Fig. 17: Malignant mixed germ cell tumour comprising of both embryonal carcinoma and yolk sac tumour of the right ovary in a 28 year-old girl. Axial contrast-enhanced CT scan (A-E) show a large abdomino-pelvic mass with avid contrast uptake of the solid areas and containing large areas of low attenuation representing necrosis/ haemorrhage. Ascites is present. References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 31 of 49

32 Fig. 18: Malignant mixed germ cell tumour comprising of both embryonal carcinoma and yolk sac tumour of the right ovary in a 40 year-old woman. Axial T1-weighted MR image (A). Axial T2-weighted MR image (B). Sagittal T2-weighted MR image (C). Gadolinium-enhanced axial T1 weighted MR image (D) show an huge abdomino-pelvic mass containing haemorrhagic that show high-signal intensity on T2WI (B and C) and high-signal intensity on T1WI (A and D). Note the avid enhancement of the solid part of the mass and the large necrotic areas (D). A small amount of ascites was detected (C). Photograph of a section of the resected specimen shows a solid haemorrhagic and necrotic tumor (E). References: Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 32 of 49

33 Images for this section: Fig. 1: Dysgerminoma of the left ovary in a 12-year-old girl. Transabdominal ultrasound (A and B) and colour Doppler ultrasound (C) images show a multilobulated solid adnexal mass with heterogeneous echogenicity and with prominent fibrovascular septa. A central necrotic component is seen on axial non-enhanced CT (D and E, arrows). Ultrasound from Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. CT from Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 33 of 49

34 Fig. 2: Dysgerminoma of the left ovary in a 12-year-old girl. Axial T2-weighted MR images (A-C). Axial T1-weighted MR image (D). DWI MR image (E). Gadolinium-enhanced fatsuppressed sagittal T1-weighted MR image (F). Sagittal T2-weighted MR image (G). The MR images of the same patient as previous show a multilobulated abdomino-pelvic mass with intermediate-signal intensity on T2WI (A-C and G) and low-signal intensity on T1WI (D). The mass show marked homogenous enhancement except the necrotic component which does not enhance (F). Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 34 of 49

35 Fig. 3: Bilateral dysgerminoma in a 18-year-old girl. Sagittal T2-weighted MR image (A and B). Sagittal T1-weighted MR image (C). Axial T2-weighted MR image (D). Axial contrast-enhanced CT image (E). Bilateral large, well-delineated solid lesion of the ovary. They display predominantly intermediate-signal intensity on T2WI (A, B and D) and lowsignal intensity on T1WI (C). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 35 of 49

36 Fig. 4: Dysgerminoma of the right ovary in a 20-year-old woman. Transabdominal ultrasound (A), axial non-enhanced CT (B) and axial contrast-enhanced CT (C) images demonstrate a multilobulated solid mass. Dionisio T. Department of Radiology, Hospital de Braga, Braga/Portugal. Fig. 5: Sagittal T2-weighted MR image (A), coronal T2-weighted MR image (B), coronal T1-weighted MR image (C), axial T2-weighted MR image (D) and gadolinium-enhanced fat-suppressed axial T1-weighted MR image (E) of the same patient as previous show a large multilobulated solid mass of the right ovary that displays predominantly intermediate-signal intensity on the T2WI (A, B and D) and low-signal intensity on T1WI (C). Dionisio T. Department of Radiology, Hospital de Braga, Braga/Portugal. Page 36 of 49

37 Fig. 6: Yolk sac tumour of the right ovary in a 21-year-old woman. Transabdominal ultrasound images (A and B) demonstrate a complex adnexal mass. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 7: Yolk sac tumour of the left ovary in a 13-year-old woman. Contrast-enhanced CT scan (A and B) show a multilobulated pelvic mass that extends into the abdomen with both solid and cystic components, giving the tumour an honeycombed appearance. There is an avid irregular enhancement of the solid portions (blue arrow). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 37 of 49

38 Fig. 8: Yolk sac tumour of the right ovary in a 25 year-old woman. Contrast-enhanced CT scan (A and B) show a lobulated adnexal mass with an avid enhancement of the solid areas (blue arrows) and with central necrosis (blue asterisk). Ascites is present. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 10: Embryonal carcinoma. Axial contrast-enhanced CT scan (A and B) demonstrates a large predominantly solid tumour with areas of necrosis/haemorrhage (red asterisk) and with speckled calcifications (red arrows). Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 38 of 49

39 Fig. 11: Immature teratoma of the right ovary in a 11 year-old-girl. Ultrasound transabdominal images (A and B) demonstrate a predominantly solid mass with cystic components. Note the presence of highly echogenic material producing posterior acoustic shadowing suggestive of intratumoral calcifications (green arrow). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 39 of 49

40 Fig. 12: Grade 2 immature teratoma of the right ovary in a 24 year-old girl. Axial contrastenhanced CT scan (A and B), sagittal contrast-enhanced CT scan (C) and coronal contrast-enhanced CT scan (D) show an heterogeneous large mass of the right ovary, with enhancing solid areas/septa and cystic/haemorrhagic components. Areas of fat attenuation are seen (green arrowheads) as well as scattered calcifications (arrows). Photograph of the gross specimen (E). CT from Ramalho M. Department of Radiology, Hospital Garcia da Orta, Almada/ Portugal. Gross specimen from Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 13: Grade 2 immature teratoma of the right ovary in a 24 year-old girl. Axial T1weighted MR image (A), axial T2-weighted MR image (B), coronal T2-weighted MR image (C), sagittal T2-weighted MR image (D) of the same patient as previous, show an heterogeneous large mass of the right ovary, with cystic components. Gadoliniumenhanced fat-suppressed axial T1 weighted MR image (E), confirms the presence of enhancing solid components and multiple septa. Photograph of a detail of the gross specimen (F). MR from Lourenço AR. Department of Radiology, Hospital Garcia da Orta, Almada/ Portugal. Gross specimen from Department of Pathology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 40 of 49

41 Fig. 14: Grade 3 immature teratoma of the right ovary in a 12 year-old girl and its mature cystic teratoma appearance after chemotherapy (retroconversion phenomenon). Coronal contrast-enhanced CT scan (A), axial contrast-enhanced CT scan (B), coronal non-contrast-enhanced CT scan (C) and axial non-contrast-enhanced CT scan (D). An enormous heterogeneous mass containing calcifications and extensive foci of fat is shown (A and B). Figures C and D show the "retroconversion phenomenon" of the immature teratoma and of its peritoneal implants after chemotherapy taking the appearance of a mature cystic teratoma. Conceição e Silva JP. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 41 of 49

42 Fig. 15: Squamous cell carcinoma arising from a mature cystic teratoma of the right ovary in a 54 year-old-woman. Contrast-enhanced CT scan (A-C), transabdominal ultrasound (D), sagittal T2-weighted MR image (E), axial T1-weighted MR image (F), gadolinium fat-supressed axial T1-weighted MR image (G). Transabdominal ultrasound (D) demonstrates a huge cystic mass with thin septation and a round echogenic nodule that on axial contrast-material CT scan (A-C) shows a fat-fluid level (orange arrowhead) and a Rokitansky nodule (orange asterisks). The area that demonstrates fat attenuation shows high-signal intensity on T1WI (F) and demonstrates saturation on fat-supressed image (G) (orange arrowheads). An irregularly marginated soft tissue component is seen in the wall of the mature teratoma (orange arrows), that was proven to be a squamous cell carcinoma. It has low-signal intensity on both T1WI and T2WI (E and F), showing avid enhancing after administration of gadolinium (G, orange arrows). An obtuse angle between the enhanced soft tissue component and the inner wall is seen (F and G, green arrows). Photograph of a section of the gross specimen showing squamous cell carcinoma in the cystic wall (H). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 42 of 49

43 Fig. 16: 71-year-old female patient with an ovarian lesion containing thyroid follicles and foci of papillary carcinoma, most probably representing a papillary carcinoma arising in a struma ovarii. Transabdominal ultrasound images (A and B), axial T1-weighted MR image (C), fat-supressed axial T2-weighted MR image (D) and sagittal T2-weighted MR image (E) show a complex-appearing mass containing solid and cystic areas. The cystic areas show variable signal intensity ("stain glass appearance") and thick septations (CE). Multiple signal voids are seen within the mass (D, arrow). Ascites is present (D and E, asterisks). Leite I, Cunha TM, Figueiredo JP, Félix A. Papillary carcinoma arising in struma ovarii versus ovarian metastasis from primary thyroid carcinoma: a case report and review of the literature. Radiology Case Oct; 7(10): Page 43 of 49

44 Fig. 17: Malignant mixed germ cell tumour comprising of both embryonal carcinoma and yolk sac tumour of the right ovary in a 28 year-old girl. Axial contrast-enhanced CT scan (A-E) show a large abdomino-pelvic mass with avid contrast uptake of the solid areas and containing large areas of low attenuation representing necrosis/haemorrhage. Ascites is present. Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 44 of 49

45 Fig. 18: Malignant mixed germ cell tumour comprising of both embryonal carcinoma and yolk sac tumour of the right ovary in a 40 year-old woman. Axial T1-weighted MR image (A). Axial T2-weighted MR image (B). Sagittal T2-weighted MR image (C). Gadolinium-enhanced axial T1 weighted MR image (D) show an huge abdomino-pelvic mass containing haemorrhagic that show high-signal intensity on T2WI (B and C) and high-signal intensity on T1WI (A and D). Note the avid enhancement of the solid part of the mass and the large necrotic areas (D). A small amount of ascites was detected (C). Photograph of a section of the resected specimen shows a solid haemorrhagic and necrotic tumor (E). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Fig. 9: Embryonal carcinoma of the right ovary in a 11 year-old girl. Transabdominal pelvic ultrasound image (A). Contrast-enhanced CT image (B) shows a very large solid right adnexal containing low-attenuating areas indicative of necrosis or haemorrhage (red asterisks). Note the presence of peripheral calcifications (red arrow). Department of Radiology, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon/Portugal. Page 45 of 49

46 Conclusion A large and predominantly solid ovarian mass in a young woman should raise suspicion of a malignant germ cell tumour. The rarity of malignant germ cell tumours contributes to a low index of suspicion, therefore a thorough knowledge of their imaging findings and diagnostic clues are important for guiding trainees and general radiologists establishing the diagnosis. Page 46 of 49

47 Personal information Mariana Horta Department of Radiology Centro Hospitalar Lisboa Ocidental Estrada do Forte do Alto do Duque Lisboa Portugal Teresa Margarida Cunha Department of Radiology Instituto Português de Oncologia de Lisboa Francisco Gentil R. Prof. Lima Basto Lisboa Portugal Page 47 of 49

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