Ovarian Malignant Germ Cell Tumors: Cellular Classification and Clinical and Imaging Features 1

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1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at Ovarian Malignant Germ Cell Tumors: Cellular Classification and Clinical and Imaging Features WOMEN S IMAGING Akram M. Shaaban, MBBCh Maryam Rezvani, MD Khaled M. Elsayes, MD Henry Baskin, Jr, MD Amr Mourad, MD Bryan R. Foster, MD Elke A. Jarboe, MD Christine O. Menias, MD Abbreviations: b-hcg = human chorionic gonadotropin, H-E = hematoxylin-eosin, LDH = lactic dehydrogenase, OMGCT = ovarian malignant germ cell tumor RadioGraphics 2014; 34: Published online /rg Content Codes: 1 From the Department of Diagnostic Radiology (A.M.S., M.R.) and Department of Radiology, Primary Children s Medical Center (H.B.), University of Utah, 30 N 1900 E, Room 1A71, Salt Lake City, UT 84132; Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, Tex (K.M.E.); Department of Diagnostic Radiology, VA Pittsburgh Healthcare System, Pittsburgh, Pa (A.M.); Department of Diagnostic Radiology, Oregon Health & Science University, Portland, Ore (B.R.F.); Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah (E.A.J.); and Department of Radiology, Mayo Clinic, Scottsdale, Ariz (C.O.M.). Presented as an education exhibit at the 2012 RSNA Annual Meeting. Received August 25, 2013; revision requested October 23 and received October 29; accepted November 22. For this journal-based SA-CME activity, the authors, editor, and reviewers have no relevant relationships to disclose. Address correspondence to A.M.S. ( akram.shaaban@hsc.utah.edu). SA-CME LEARNING OBJECTIVES After completing this journal-based SA- CME activity, participants will be able to: List the different types of OMGCTs and describe their demographic, pathologic, and clinical characteristics. Discuss the imaging manifestations of the different types of OMGCTs. Describe how to create a reasonable differential diagnosis on the basis of clinical and imaging features. See Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient s age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. RSNA, 2014 radiographics.rsna.org Introduction Germ cell tumors are a histologically heterogeneous group of tumors that share a common origin: the primitive germ cell of the embryonic gonad (1). They constitute about 20% 25% of all ovarian neoplasms; however, only 5% of germ cell tumors are malignant, with most (95%) being benign mature cystic teratomas (1). Ovarian malignant germ cell tumors (OMGCTs) include, in order of frequency, dysgerminomas, immature teratomas, yolk sac tumors, and mixed germ cell tumors. Other less common OMGCTs include embryonal carcinomas, choriocarcinomas, and malignant struma ovarii tumors. OMGCTs

2 778 May-June 2014 radiographics.rsna.org constitute about 2.6% of malignant ovarian neoplasms, whereas ovarian epithelial neoplasms constitute about 95% (2). Recent evidence suggests that the much more common epithelial ovarian neoplasms actually originate from precursors outside the ovaries; thus, OMGCTs may, in fact, be the most common primary ovarian malignant neoplasms (3,4). According to Surveillance, Epidemiology, and End Results (SEER) data, the 30-year age-adjusted incidence of OMGCTs per 100,000 women-years is (2,5). OMGCTs occur in various age groups, with the highest incidence in those years old (5). In the first 2 decades of life, more than 60% of ovarian tumors are of germ cell origin, and one-third of these are malignant (6). In this article, we discuss the cellular classification, imaging features, patterns of spread, staging, and management of OMGCTs using a modified version of the current 2003 World Health Organization classification system (Table 1) (7). Clinical Manifestation There are major clinical differences between OMGCTs and the more common ovarian epithelial carcinoma (Table 2). OMGCTs tend to be large at the time of diagnosis and progress rapidly. They typically manifest in adolescence with abdominal pain (in 87% of patients) and an abdominal mass (in 85% of patients). About 10% of patients present with an acute abdomen resulting from torsion, hemorrhage, or tumor rupture (which is more common with yolk sac tumors or mixed germ cell tumors). Less common symptoms include abdominal distention, fever, and vaginal bleeding. Duration of symptoms is usually short, with a median of 2 4 weeks (8). Usually, OMGCTs are unilateral, but they may be bilateral in about 4.3% of patients. Bilaterality is more common with dysgerminomas and mixed germ cell tumors with pure nondysgerminoma cell lines (9). Uncommonly, patients may present with endocrinal manifestations resulting from hormone production by tumor cells, including menstrual irregularities and isosexual precocity, which results from human chorionic gonadotropin (b-hcg) secretion or carcinoid syndrome from serotonin secretion (Table 2). Tumor Markers Various tumor markers are elevated depending on the component tissues of OMGCTs (Table 3). Elevated serum tumor marker levels may serve as an adjunct in initial diagnosis, therapy monitoring, and posttreatment surveillance (Table 3). Alpha-fetoprotein and b-hcg are found in all patients with a tumor that contains components of a yolk sac tumor and choriocarcinoma, respectively. Elevated a-fetoprotein or b-hcg levels are Table 1: Cellular Classification of OMGCTs Primitive germ cell tumors Dysgerminoma, yolk sac tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, mixed germ cell tumors Bi- or triphasic teratoma Immature teratoma, mature cystic teratoma with malignant transformation Monodermal teratoma Malignant struma ovarii, malignant carcinoid, other malignant lesions Source. Reference 7. virtually diagnostic of OMGCTs and should be measured in all young women who present with a pelvic mass. Dysgerminomas produce low levels of b-hcg in 5% of cases because of the presence of multinucleated syncytiotrophoblastic giant cells; they also occasionally produce lactic dehydrogenase (LDH). Both embryonal carcinoma and polyembryoma may produce a-fetoprotein and b-hcg, most commonly the former. Serum a-fetoprotein concentrations are significantly elevated at diagnosis in most ovarian immature teratomas with foci of yolk sac tumor and are occasionally mildly elevated in immature teratomas without yolk sac tumor (10). Mixed germ cell tumors may secrete b-hcg, a-fetoprotein, or both, depending on the components. Eighty-eight percent of ovarian germ cell tumors have increased serum lactic dehydrogenase isoenzyme-1 (11,12). Characteristic Features of OMGCTs Dysgerminoma Dysgerminoma is the ovarian counterpart to testicular seminoma. It is the most common OMGCT, accounting for 1% 2% of primary ovarian neoplasms and 32.8% 37.5% of all OMGCTs (5,13,14). According to a survey performed in the United States comprising 1262 cases of OMGCTs registered from 1973 to 2002, the age-adjusted incidence of ovarian dysgerminoma per 100,000 women-years was (5). Most cases occur in adolescence and early adulthood, although it may occur at any age, with reported cases ranging from 7 months to 70 years old (13). Most patients are symptomatic and present with pain, bloating, and menstrual disorders. Pure dysgerminomas do not secrete hormones; however, 5% of tumors contain syncytiotrophoblasts, which produce b-hcg. Serum lactic dehydrogenase and alkaline phosphatase are often nonspecifically elevated. There is an increased

3 RG Volume 34 Number 3 Shaaban et al 779 Table 2: Major Differences Between Malignant Ovarian Epithelial and Germ Cell Tumors Characteristic Epithelial Tumors Germ Cell Tumors Prevalence Much more common Less common Age affected Primarily older women* Primarily girls and young women Race affected More common in white women More common in black and Asian women Laterality Malignant serous, mucinous, clear cell, and endometrioid tumors are bilateral in 57.5%, 21.3%, 13.3%, and 26.8% of patients, respectively Usually unilateral, but may be bilateral in about 4.3% of patients Tumor markers CA-125 a-fetoprotein and b-hcg Endocrinal No May result from hormonal production manifestations 5-year survival rate 44% overall, depending on tumor stage 100% for dysgerminoma and 85% for other malignant germ cell tumors *Fifty percent of all cases occur in women older than 65 years. Table 3: Tumor Markers Expressed by Each Histologic Subtype of OMGCTs Histologic Subtype AFP b-hcg LDH Dysgerminoma ±* + Yolk sac tumor + + Immature teratoma ± ± Mixed germ cell ± ± ± tumor Choriocarcinoma + ± Embryonal carcinoma ± ± ± Polyembryoma ± + Note. AFP = a-fetoprotein, b-hcg = human chorionic gonadotropin, LDH = lactic dehydrogenase, ± = may be present, = not present, + = present. *Low levels of b-hcg are seen in dysgerminomas with nondysgerminomatous elements or syncytiotrophoblasts. Figure 1. Dysgerminoma. Photomicrograph (original magnification, 200; hematoxylin-eosin [H-E] stain) shows variably sized nests of cells that resemble primordial germ cells and are separated by fibrous septa, which contain mature lymphocytes. incidence of dysgerminomas that arise in the dysgenetic gonads of 46, XY patients with pure (or complete) gonadal dysgenesis (15). Gross Pathologic Features. Ovarian dysgerminomas are characteristically solid and well encapsulated, with a mean diameter of 15 cm. At sectioning, they are lobulated, soft, fleshy, and gray-white or light tan. Areas of coagulative necrosis and hemorrhage that are typically associated with cystic change may be seen. Dysgerminomas may be bilateral, with gross involvement of the contralateral ovary in 6.5% 10% of cases (1,9). Microscopic Pathologic Features. The microscopic appearance of ovarian dysgerminomas is characteristic and identical to that of testicular seminomas (Fig 1). Ovarian dysgerminomas are composed of a uniform population of round cells that resemble primordial germ cells in welldefined nests, are separated by fibrous strands, and are infiltrated by T lymphocytes. The cells have clear to eosinophilic cytoplasm and a central large round or flattened nucleus that contains one or a few prominent nucleoli. Mitoses are often numerous (16). Imaging Features. With few exceptions, dysgerminomas are characteristically purely solid. At ultrasonography (US), they are divided into component lobules, with heterogeneous echogenicity, smooth lobulated contours, and well-defined borders, and they are richly vascularized at color and power Doppler US (Fig 2) (17 19). The lobular pattern is also seen at computed tomography

4 780 May-June 2014 radiographics.rsna.org Figure 2. Dysgerminoma in a 12-yearold girl. Transvaginal gray-scale (a) and duplex Doppler (b) US images of the right ovary show a solid ovarian mass (arrows) with prominent blood flow. (CT), which depicts a predominantly solid tumor, with enhancing septa and areas of cystic change that may represent hemorrhage or necrosis (Fig 3) (18,20). Calcifications may be present in a speckled pattern (18). The most characteristic appearance at magnetic resonance (MR) imaging is that of a solid mass divided into lobules by fibrovascular septa (Fig 4). Dysgerminomas have low signal intensity relative to muscle on T1-weighted images and are isointense or slightly hyperintense on T2-weighted images. Usually, septa are hypoor isointense on T2-weighted images and are difficult to appreciate on T1-weighted images, with intense enhancement after administration of contrast material (18,20). Septa may be hyperintense on T2-weighted images when major edematous changes are present (Fig 5) (18). Multilocular cystic masses with papillary projections and irregular septations that mimic epithelial ovarian neoplasms have also been described (21). Yolk Sac Tumor Ovarian yolk sac tumors, formerly known as endodermal sinus tumors, are the third most common OMGCTs, accounting for approximately 1% of ovarian malignancies and 14.5% 16.4% of all OMGCTs. They are most common in women in the second and third decades of life and are rare in women over 40 years old (22). Gross Pathologic Features. Yolk sac tumors are large encapsulated masses with a mean diameter of 15 cm and usually have a smooth external surface. In cross section, they charac- Figure 3. Dysgerminoma in a 16-year-old girl. Axial contrast-enhanced CT image shows a large lobulated solid mass (arrows) in the right ovary. Enhancing septa (arrowheads) divide the mass into lobules. teristically have mixed solid and cystic components. The solid components are soft gray to yellow, with extensive areas of hemorrhage and necrosis. Cysts vary from a few millimeters to 2 cm in diameter and are diffusely scattered throughout the tissue, giving the neoplasm a soft, wet, honeycombed appearance. Capsular tears have been described at pathologic examination and occur in 27% of cases (22). Yolk sac tumors are bilateral in less than 5% of patients, and the contralateral ovary contains a dermoid

5 RG Volume 34 Number 3 Shaaban et al 781 Figure 4. Ovarian dysgerminoma and mature cystic teratoma in a 21-year-old woman. Coronal (a) and sagittal (b) T2-weighted, axial T1-weighted (c, d), and axial contrast-enhanced fat-suppressed T1- weighted (e, f) MR images show a multilobulated mass (arrows) in the right ovary. The mass is predominantly hyperintense relative to muscle on T2-weighted images and isointense on T1-weighted images. Hypointense septa separate the mass into individual lobules. An associated mature cystic teratoma (*) is also seen.

6 782 May-June 2014 radiographics.rsna.org Figure 5. Ovarian dysgerminoma in a 17-year-old girl. Coronal T2-weighted MR image shows a multilobulated mass (arrows) in the left ovary. The mass is predominantly isointense relative to muscle, and hyperintense septa separate the mass into individual lobules. Figure 6. Yolk sac tumor. Photomicrograph (original magnification, 200; H-E stain) shows a Schiller-Duval body, which is characterized by a papilla with a fibrovascular core and a peripheral covering of primitive epithelial cells. cyst in about 10% of cases (16,22). They may grow very rapidly. In their review of 71 cases of ovarian yolk sac tumor, Kurman and Norris (22) described two patients who had normal findings at pelvic examinations 4 weeks before their tumors (9 cm and 12 cm in greatest diameter) were discovered. They also described another woman who was monitored at regular intervals from the beginning of her pregnancy and who developed a 23-cm tumor by the time oophorectomy was performed at 14 weeks gestation. This rapid rate of growth may explain the high rate of capsular tears observed at surgery and pathologic examination. Microscopic Pathologic Features. Yolk sac tumors are germ cell tumors with a cellular structure that resembles that of the primitive yolk sac (the vitelline elements). The term yolk sac tumor is more inclusive than the original term (endodermal sinus tumor) and better describes the different microscopic patterns these tumors demonstrate. Although these histologic patterns considerably differ from each other, they are frequently observed within the same tumor. Ten different histologic patterns may be observed in yolk sac tumors: microcystic, endodermal sinus, solid, alveolar-glandular, polyvesicular vitelline, myxomatous, papillary, macrocystic, hepatoid, and glandular. Schiller-Duval bodies are the most characteristic feature of yolk sac tumors and are composed of isolated papillary projections with a central blood vessel and a peripheral sleeve Figure 7. Yolk sac tumor in a 26-year-old woman with elevated a-fetoprotein levels. Transabdominal color Doppler US image shows a mixed solid and cystic mass (arrows) in the right ovary. The solid component is heterogeneous and contains small vascular spaces (arrowheads), a finding referred to as the bright dot sign. of embryonic epithelial cells (Fig 6). The presence of Schiller-Duval bodies may be considered diagnostic of yolk sac tumor; however, in some cases, they may be poorly represented, atypical, or absent. Their absence does not preclude a diagnosis of yolk sac tumor if the tumor appearance is otherwise typical (1). Imaging Features. The reported imaging findings of yolk sac tumors include a unilateral enhancing mixed solid and cystic mass with a hemorrhagic portion. The outer contour is usually

7 RG Volume 34 Number 3 Shaaban et al 783 Figure 8. Ovarian yolk sac tumor in an 18-year-old girl with elevated a-fetoprotein levels. Axial (a, b) and coronal (c) contrast-enhanced CT images show a large abdominal mixed solid and cystic mass, with small foci of enhancement (black arrows in a and b), a finding known as the bright dot sign that indicates increased tumor vascularity, and a capsular tear (white arrow in b and c), a finding that is frequently seen in the pathologic specimens of yolk sac tumors. a = ascites. smooth (23 26). At US, the solid components have heterogeneous echogenicity, and the cystic spaces are divided by septa (Fig 7) (26). The bright dot sign is a common finding and is seen at contrast-enhanced CT and MR imaging as enhancing foci in the wall or solid components. These foci of enhancement are attributed to dilated vessels, considering the highly vascular nature of these tumors (Fig 8). Although it is common, the bright dot sign is not pathognomonic for yolk sac tumor because other germ cell tumors may exhibit similar morphologic characteristics (27). Another imaging feature described in yolk sac tumors is capsular tears, which correspond to those seen at pathologic examination (Fig 6) (27). Although they are commonly seen in yolk sac tumors, these tears are not pathognomonic because other ovarian tumors, including benign lesions such as mature cystic teratomas, may demonstrate capsular tearing (25). Areas of hemorrhage have high signal intensity on T1-weighted MR images. Immature Teratoma Immature teratoma is considered the second most common OMGCT, accounting for 35.6% 36.2% of all cases. It is responsible for 30% of deaths from ovarian cancer in women younger than 20 years old (5,14). Its peak incidence is between 15 and 19 years of age, and it rarely occurs in menopause. Similar to mature cystic teratomas (dermoid cysts), immature teratomas consist of tissues derived from the three germ cell layers: ectoderm, mesoderm, and endoderm. However, immature teratomas differ from mature cystic teratomas in that they contain immature or embryonic tissue. Furthermore, immature teratomas typically affect younger patients (usually in the first 2 decades of life), exhibit malignant behavior, and are associated with a poorer prognosis. Gross Pathologic Features. Typically, immature teratomas are larger (14 25 cm) than mature cystic teratomas (mean, 7 cm) (28,29). Most immature teratomas are seen as an encapsulated mass that is predominantly solid, soft, and fleshy at sectioning. Small cysts may be present. Usually, cystic areas are filled with serous, mucinous fluid, or fatty sebaceous material. The cut surface is multinodular and brown to pink or gray to white. Frequently, areas of necrosis and hemorrhage are present. Fat, hair, and sebaceous material may

8 784 May-June 2014 radiographics.rsna.org Figure 9. Immature teratoma. Photomicrograph (original magnification, 100; H-E stain) shows immature neuroectoderm composed of embryonicappearing neuroepithelial tubules (arrowhead). Cartilage (arrow) is also seen. be seen (30). A dermoid cyst is grossly identified within the immature cystic teratoma in as many as 26% of cases or in the contralateral ovary in as many as 10% of cases (31). Microscopic Pathologic Features. Tissues that derive from the three germ layers are seen, with a variable admixture of mature and immature elements. The presence of immature elements establishes the diagnosis. The grading system for immature teratomas is based on the amount of immature neuroepithelium present, the most common tissue in immature teratomas (Fig 9) (30). Imaging Features. At US, immature teratomas are nonspecific and resemble other solid ovarian neoplasms, appearing as a heterogeneous solid mass with scattered small calcifications. Small foci of fat may be difficult to appreciate, whereas larger fat components appear as areas of increased echogenicity (Fig 10) (23,32). At MR imaging and CT, immature teratomas appear as a predominantly solid mass with fatty elements, coarse irregular calcifications, and numerous cysts of variable sizes. The solid component has soft-tissue attenuation at CT and exhibits a wide variety of signal intensities at T2-weighted MR imaging. Foci of fat that are much smaller than those seen in mature cystic teratomas are typically seen interspersed within the solid mass and may be seen at MR imaging with the use of fat-suppression techniques (Fig 11) (33). Fatty fluid may also be seen within cystic compartments. Unlike mature cystic teratomas, in which cysts predominantly contain fatty sebaceous fluid, in immature teratomas, cysts predominantly have attenuation and signal intensity similar to those of simple fluid (33). And in immature teratomas, calcifications Figure 10. Immature teratoma in a pregnant 22- year-old woman. Transabdominal gray-scale (a) and color Doppler (b) US images of the right ovary show a solid heterogeneous mass (arrows) with patchy areas of increased echogenicity (arrowheads in a) that represent foci of fat and small echogenic foci with acoustic shadowing (arrowhead in b) that represent calcifications. are small, irregular, and scattered throughout the tumor, whereas in mature cystic teratomas, they are typically coarse or toothlike and located in the mural nodule or cyst wall. There is no significant correlation between the amount of solid tissue and histologic tumor grade (33). Growing teratoma syndrome was described by Logothetis et al (34) and consists of an enlarging teratoma that contains mature elements that arise during or after chemotherapy for treatment of a nonseminomatous germ cell tumor in patients with normal serum a-fetoprotein and b-hcg levels (Fig

9 RG Volume 34 Number 3 Shaaban et al 785 Figure 11. Ovarian immature teratoma in a 28-year-old woman. Axial contrast-enhanced CT image shows a large predominantly solid abdominal mass interspersed with small foci of fat (white arrows) and calcifications (black arrows). Figure 12. Growing teratoma syndrome in a 29-year-old woman who underwent resection of an ovarian immature teratoma 11 months earlier. (a) Abdominal US image shows a round echogenic mass (arrow) in the right lobe of the liver. (b) Axial contrast-enhanced CT image shows multiple liver lesions with fat attenuation (arrows). Tumor markers were normal, and pathologic analysis revealed only mature teratomatous elements. 12). It is more common in men after undergoing treatment for testicular nonseminomatous germ cell tumors than in women. In fact, only about 50 cases of growing teratoma syndrome have been described in women. Treatment of growing teratoma syndrome is similar to that of immature teratomas or mixed germ cell tumors with immature teratoma elements (35). The mechanism of evolution from an OMGCT to mature teratomatous tissue is not fully understood; however, proposed mechanisms include induction of somatic maturation in malignant cells by chemotherapy; chemotherapeutic retroconversion; and selective destruction of immature elements by chemotherapy, which leaves behind resistant mature elements. Mature Cystic Teratoma with Malignant Degeneration Mature cystic teratoma (dermoid cyst), which is composed of well-differentiated tissues that derive from all three germ-cell layers (ectoderm, mesoderm, and endoderm), is the most common benign ovarian neoplasm, with a peak incidence between 20 and 40 years of age. Malignant transformation of mature cystic teratomas is rare, with a reported incidence of 0.17% 2% among those with a mature cystic teratoma, and accounts for about 2.9% of all OMGCTs (5,36 38). In contrast to immature teratomas, which manifest early in life, malignant transformation in mature cystic teratomas develops in the 6th or 7th decade

10 786 May-June 2014 radiographics.rsna.org Figure 13. Mature cystic teratoma with malignant degeneration. (a) Low-power photomicrograph (original magnification, 20; H-E stain) shows an invasive squamous cell carcinoma (arrow) arising in a mature cystic teratoma. A cyst lined by benign mature squamous epithelium is seen at left. (b) High-power photomicrograph (original magnification, 200; H-E stain) shows infiltrative nests of markedly atypical keratinizing squamous cells in the malignant component. Atypical mitotic figures (arrow) are also seen. Figure 14. Mature cystic teratoma with a squamous cell carcinoma component in a 66-year-old woman. (a, b) Transvaginal gray-scale US images show invasion (arrows) of an echogenic mass (M) into the uterus (UT). of life. Although any of the constituent tissues of a teratoma may undergo malignant transformation, squamous cell carcinoma is the most commonly associated cancer, accounting for more than 80% of cases of malignant degeneration (Fig 13). Other malignant tumors including carcinoid, thyroid and basal cell carcinoma, intestinal adenocarcinoma, melanoma, leiomyosarcoma, angiosarcoma, and chondrosarcoma may arise (39). The Rokitansky protuberance is a common site for malignant change. It has been suggested that squamous cell carcinoma in mature cystic teratoma arises from squamous metaplasia of columnar epithelium (40). Findings associated with malignant transformation include a patient age over 45 years, tumor diameter of more than 10 cm, and serum squamous carcinoma antigen level above 2 ng/ ml (41,42). Serum squamous carcinoma antigen has been well used as a tumor marker in patients with squamous cell carcinoma and is elevated in 81.3% of patients who develop squamous cell carcinoma in mature cystic teratoma (43). The typical imaging finding of an ovarian teratoma is a cystic mass with intratumoral fat. The Rokitansky nodule or dermoid plug, a common finding in mature cystic teratoma, is described as a protrusion arising from the inner surface of a cyst

11 RG Volume 34 Number 3 Shaaban et al 787 Figure 15. Mature cystic teratoma with a squamous cell carcinoma component in a 72-year-old woman. Axial contrast-enhanced CT images show a large pelvic mass with large fat lobules (*) and nodular calcifications (black arrows). An enhancing soft-tissue component envelops the fat lobules and demonstrates transmural spread (white arrows in b). that contains hair, teeth, and fat. In typical cases, in which intralesional fat or a tooth may be seen, malignant transformation may be easily diagnosed if a heterogeneously irregular solid component is present with transmural extension and invasion of adjacent organs. Transmural tumor extension may be depicted at US, CT, or MR imaging (Figs 14 16). The mere presence of enhancement of solid components does not always indicate malignancy but probably reflects the heterogeneity of tissues, which may contain enhancing elements (eg, thyroid tissue) (44,45). About 6% of mature cystic teratomas do not have fat in the lumen or cyst wall and appear as fluid-containing cystic lesions (46). In these lesions, malignant transformation results in a cystic mass with enhancing mural components that is indistinguishable from other malignant ovarian cystic neoplasms (Fig 17). The presence of an obtuse angle between the soft tissue and inner wall of the cyst is a common imaging finding of malignant transformation of ovarian teratomas (47,48). Pseudomyxoma peritonei is a clinical syndrome that is characterized by mucinous ascites and implants that diffusely involve the peritoneal surfaces. There is compelling evidence, on the basis of immunohistochemical and molecular genetic techniques, that in most cases, the source is an appendiceal mucinous tumor (49,50). The only exception appears to be the rare case of ovarian pseudomyxoma peritonei caused by a mucinous tumor, cystadenoma, tumor with low malignant potential, or invasive carcinoma that arises in ovarian mature cystic teratoma (51 53). The imaging features of pseudomyxoma peritonei are those of a mature cystic teratoma with a prominent solid component, a large volume of ascites with selective sparing of the small bowel and its mesentery, and scalloping of the liver surface (Figs 18, 19) (54 57). The mucin-producing cells in pseudomyxoma peritonei are poorly adherent and circulate with peritoneal fluid. They are easily dislodged from the bowel surface by peristalsis and only seed at sites of relative stasis, which explains the selective sparing of the surface of the small bowel and mesentery (57). The development of malignant transformation in a mature cystic teratoma should be differentiated from an ovarian collision tumor, which is defined as a tumor with two adjacent but histologically distinct tumors with no histologic admixture at the interface. Ovarian collision tumors are most commonly composed of teratoma and cystadenoma or cystadenocarcinoma. With collision tumors, normal ovarian tissue may usually be identified intervening between both tumors at imaging, and there is no histologic admixture at the interface (58). On the other hand, tumors occurring in mature cystic teratomas develop in the Rokitansky nodule within the lesion and may extend through the wall into the surrounding tissues. Nongestational Choriocarcinoma Choriocarcinoma is among the rarest of the gonadal germ cell tumors, with pure examples accounting for 2.1% 3.4% of all OMGCTs

12 788 May-June 2014 radiographics.rsna.org Figure 16. Mature cystic teratoma with a squamous cell carcinoma component in a 66-year-old woman. Axial T2-weighted (a), axial T1-weighted (b), axial T1-weighted fat-suppressed (c), sagittal T2- weighted (d), axial contrast-enhanced T1-weighted fat-suppressed (e), and sagittal contrast-enhanced T1-weighted fat-suppressed (f) MR images show a pelvic mass with a fluid-fluid level. The upper layer (F) of the mass has signal characteristics of fat: that is, high signal intensity on T1- and T2-weighted images and low signal intensity on T1-weighted fat-suppressed images. The dependent layer (B) of the mass has signal characteristics of blood, with high signal intensity on T1-, T2-, and T1-weighted fat-suppressed images. An enhancing soft-tissue mural nodule (arrows) with transmural extension and invasion of the uterus is also seen.

13 RG Volume 34 Number 3 Shaaban et al 789 Figure 17. Mature cystic teratoma with a squamous cell carcinoma component in a 63-year-old woman. Axial contrast-enhanced CT images show a right ovarian cystic mass (C) with an enhancing peripheral soft-tissue component (arrows in a). No fat is present in the mass, but there is minimal cyst wall calcification (arrow in b). Figure 18. Pseudomyxoma peritonei in a 45-year-old woman with a mature cystic teratoma in the right ovary. Axial contrast-enhanced CT image shows a fat-containing mass (arrow) in the right ovary, a finding indicative of a mature cystic teratoma, and distention of the abdomen by a large amount of ascites (A). A low-grade malignant mucinous intestinal-type ovarian tumor arising in a mature cystic teratoma was seen at pathologic analysis. (5,14). The presence of an adnexal mass in association with an elevated b-hcg level in patients of reproductive age may cause clinical confusion and an erroneous diagnosis of ectopic pregnancy, a more common condition than ovarian choriocarcinoma (59). Figure 19. Pseudomyxoma peritonei in a 53-yearold woman with a history of ruptured mature cystic teratoma that contained a low-grade malignant mucinous intestinal-type tumor in the right ovary. Axial contrast-enhanced CT image shows scalloping of the liver capsule (arrows) and tumor in the fissure of the ligamentum venosum (arrowhead). Microscopic Pathologic Features. The typical pattern of choriocarcinoma is a plexiform arrangement of syncytiotrophoblast cells with mononucleated, mostly cytotrophoblast, cells around foci of hemorrhage, although some cases have a relatively inconspicuous syncytiotrophoblast component (Fig 20). Ovarian tumors should be distinguished from metastatic gestational choriocarcinoma; a concomitant or proximate gestation almost always indicates gestational choriocarcinoma, whereas another germ cell tumor component indicates a primary ovarian tumor (60).

14 790 May-June 2014 radiographics.rsna.org Figure 20. Nongestational choriocarcinoma. Photomicrograph (original magnification, 200; H-E stain) shows a mixed population of syncytiotrophoblasts (arrow) and cytotrophoblasts (arrowhead), a finding indicative of abundant hemorrhage and necrosis. Figure 21. Ovarian nongestational choriocarcinoma in a 27-year-old woman who presented with a palpable pelvic mass and b-hcg level of 217,000 miu/ml. Coronal T1-weighted (a), sagittal T2- weighted (b), and axial contrast-enhanced T1- weighted gradient-echo (c) MR images show a large pelvic mass (arrows) that is slightly hypointense relative to muscle on T1-weighted images and small cystic cavities that are best seen on T2-weighted images. Soft-tissue septa (arrowheads) between the cystic cavities demonstrate enhancement on contrast-enhanced images. Imaging Features. Few reports are available on the imaging characteristics of nongestational choriocarcinoma. However, a well-defined mixed-echogenicity adnexal mass at pelvic US has been described. US helps exclude uterine or ectopic pregnancy in patients with high levels of b-hcg. Reported CT features of nongestational choriocarcinoma include an enhancing highly vascular solid mass. Abnormal large signal voids that represent vascular structures and small cystic cavities are seen in solid components at T2- weighted MR imaging, and high-signal-intensity foci, a result of hemorrhage, may be seen in solid portions at T1-weighted MR imaging (Fig 21). Substantial uptake of gadolinium-based contrast material in solid portions is suggestive of a highly vascularized tumor (61).

15 RG Volume 34 Number 3 Shaaban et al 791 Figure 22. Embryonal carcinoma. Photomicrograph (original magnification, 200; H-E stain) shows a sheet of large primitive cells with scattered gland- and slitlike spaces between them. The cells are large and pleomorphic with vesicular nuclei and prominent nucleoli. Numerous mitotic figures (arrows) are also seen. Figure 23. Mixed germ cell tumor in a 24-year-old woman. Axial contrast-enhanced CT image shows a predominantly solid pelvic mass (black arrows), portions of which have fat attenuation (white arrows). Areas of soft tissue with fat loculi are also seen and suggest immature teratoma; however, histologic analysis revealed a mixed germ cell tumor composed of dysgerminoma, immature teratoma, and yolk sac elements. Embryonal Carcinoma, Polyembryoma, and Mixed Germ Cell Tumor In general, embryonal carcinomas are unilateral and large, averaging 17 cm. Macroscopically, they have a smooth outer surface, and at sectioning they are soft, with a highly variegated appearance and extensive areas of hemorrhage and necrosis. They are predominantly solid, with cystic spaces that contain mucoid material. Their appearance varies according to the number and types of components present in mixed tumors (62). Typical histologic features of embryonal carcinoma include solid sheets and nests of large primitive cells in a pseudoglandular pattern that occasionally form papillae. Typically, nuclei are large, crowded, pleomorphic, and vesicular, with prominent nucleoli (Fig 22) (60,63). Embryonal carcinomas may occur in a pure form or as a component of a mixed germ cell tumor. The most common components associated with embryonal carcinomas in mixed germ cell tumors are yolk sac tumors and dysgerminomas (62). Polyembryomas are an extremely rare OMGCT. Since they were originally described, only 15 cases have been reported in the English medical literature, none of which were in a pure form but rather as a component of mixed OMGCTs in children and young women (1,60,64). Immature teratomas and yolk sac tumors are the most commonly reported components associated with polyembryoma in mixed germ cell tumors, which occur in patients 3 44 years old (mean, 24.5 years). Serum a-fetoprotein and b-hcg may be elevated. Grossly, polyembryomas are unilateral and large, with a microcystic cut surface. Microscopically, they consist of small embryo-like bodies with central germ disks that are composed of embryonal carcinoma epithelia and two cavities: a dorsal cavity that resembles the amniotic cavity and a ventral cavity that resembles the yolk sac cavity. Embryoid bodies lie in an edematous to myxoid stroma that has prominent blood vessels (60). Ovarian mixed germ cell tumors are composed of more than one germ cell element, mainly dysgerminoma, teratoma, and yolk sac tumor, although other elements, such as choriocarcinoma, polyembryoma, and embryonal carcinoma, may be present (1). A large number of malignant elements, such as yolk sac tumor and high-grade immature teratoma, is associated with more aggressive behavior (1). To our knowledge, no reports on the imaging features of mixed OMGCTs are available. In our experience, they manifest as a solid mass with areas of cystic change resulting from hemorrhage or necrosis or a cystic lesion with solid components. Intralesional fat or calcifications may be seen if an immature teratoma element is present (Fig 23). Malignant Struma Ovarii Although thyroid tissue may be found in 5% 20% of mature cystic teratomas at histopathologic analysis, the term struma ovarii should be reserved for those rare ovarian tumors that are composed entirely or predominantly of thyroid tissue (1). As such, struma ovarii may manifest

16 792 May-June 2014 radiographics.rsna.org Figure 24. Malignant struma ovarii in a 37-year-old woman. Axial contrast-enhanced CT image shows a mixed solid and cystic mass with an irregular enhancing solid nodule (white arrow) arising from the right ovary (black arrows). Histologic analysis revealed struma ovarii with multiple foci of follicular carcinoma. Figure 25. Mature cystic teratoma with a malignant struma ovarii component in a 44-year-old woman. Axial contrast-enhanced CT image shows a mass (black arrow) with an enhancing solid component (*) and a thin rim of fat attenuation (white arrow) in the right ovary. Histologic analysis revealed struma ovarii with multiple foci of follicular carcinoma. in a pure form or an impure form as a component of a mature cystic teratoma that constitutes more than 50% of tumor volume. Struma ovarii account for about 2.7% of all ovarian teratomas and 0.5% of all ovarian malignant tumors (1). Malignancy is present in 5% 10% of cases (65). Often, there are no metastases or other features of malignancy, and the diagnosis is made at pathologic analysis (1). Most patients are asymptomatic or present with a pelvic mass, and approximately 5% of patients present with clinical evidence of hyperthyroidism (66). Gross Pathologic Features. Usually, struma ovarii is unilateral, and its size varies; often, it is less than 10 cm. At sectioning, compartments of amber-colored colloid separated by thick fibrous septa are seen on the cut surfaces (1). A diagnosis of malignant struma ovarii is made on the basis of its histologic type. Microscopic Pathologic Features. Struma ovarii is composed of mature thyroid tissue that consists of variably sized acini, is filled with colloid, and is lined by a single layer of columnar or flattened epithelium. Cellular atypia, nuclear pleomorphism, vascular or capsular invasion, and distant metastases are definite clues to malignant transformation of struma ovarii. Most malignant struma ovarii tumors contain follicular carcinoma; papillary, anaplastic, and Hurthle cell carcinomas have also been described (1,67). Imaging Features. In the absence of metastases or capsular invasion, no radiologic findings have been described to differentiate malignant from benign struma ovarii. Typically, struma ovarii is seen as a multilocular cystic mass with smooth margins and large cystic spaces that represent dilated thyroid follicles filled with thyroglobulin and thyroid hormones. At transvaginal US, struma ovarii typically appears as a cystic tumor with characteristic struma pearls, which are well circumscribed, vascularized, round echogenic solid areas with smooth contours (68). At unenhanced CT, struma ovarii is characterized by high-attenuation loculi, a result of iodinated thyroid hormone, and calcifications. Intense enhancement occurs after iodinated contrast material is administered (Fig 24) (69,70). Loculi with fat attenuation, which represent sebaceous material, may be seen in impure struma ovarii and indicate mature cystic teratoma elements (Fig 25). At MR imaging, the most common appearance of struma ovarii is a multilobulated complex mass with thick septa, multiple cysts with variable signal intensity, and enhancing solid components. Although the cystic components have a variety of signal intensities at MR imaging, areas of low signal intensity on T2-weighted images and high signal intensity on T1-weighted images are common and correspond to areas of high attenuation at CT (69,71). Solid components appear as thickened septa or cyst walls or

17 RG Volume 34 Number 3 Shaaban et al 793 as a mass and demonstrate enhancement after administration of gadolinium-based contrast material (71). The presence of ascites or pseudo- Meigs syndrome does not necessarily indicate malignant struma ovarii. For reasons that are not clear, benign struma ovarii can manifest with abdominal ascites or hydrothorax and may have elevated serum CA-125 levels (70,72 74). Malignant Carcinoid Primary ovarian carcinoid tumors are monodermal teratomas with differentiation toward argentaffin cells. These rare neoplasms account for about 0.5% of all carcinoid tumors and 0.1% of all malignant ovarian tumors (75). Primary ovarian carcinoid tumors are divided into five subtypes: insular, meaning it is composed of islet cells; trabecular; mucinous, meaning it is composed of goblet cells; stromal; and mixed, a combination of the four pure types (1). Mucinous carcinoids of the ovary are slightly more aggressive than other ovarian carcinoids and behave similar to mucinous carcinoid tumors of the appendix, with metastases possible at initial evaluation. Insular carcinoids are considered malignant, but they are slow growing and are only occasionally associated with metastases. Trabecular carcinoids are generally not associated with metastases; only one case of strumal carcinoid with metastases has been reported (1). Clinicopathologic features such as unilaterality and an early stage favor a primary ovarian neoplasm; however, in the absence of other teratomatous elements, it may be difficult or impossible to determine whether an ovarian carcinoid is primary or metastatic (76). In contrast to intestinal carcinoids, which are much more common and manifest with carcinoid syndrome only when liver metastases develop, about one-third of ovarian carcinoids are associated with typical carcinoid syndrome despite the absence of metastases, which may be because ovarian carcinoids drain directly into the systemic circulation, bypassing the liver, which inactivates the serotonin produced by intestinal carcinoids (1,77). Gross Pathologic Features. Carcinoids are usually a component of a mature cystic teratoma, with a similar gross appearance. When they are not associated with mature cystic teratomas, they are solid (1). Unlike metastatic carcinoids, which are usually bilateral, all primary ovarian carcinoids are unilateral (76). Carcinoids vary in size, from microscopic to 20 cm in diameter, and their color ranges from light brown to yellow or pale gray (1). Microscopic Pathologic Features. Primary ovarian insular carcinoid has the appearance of a typical midgut carcinoid: small acini and solid nests of uniform polygonal cells with abundant cytoplasm and round or oval centrally located hyperchromatic nuclei. The cytoplasm may contain red, brown, or orange argentaffin granules. Usually, the connective tissue surrounding the cell nests is dense and hyalinized because of the fibrogenic effect of serotonin, which is produced by the tumor (1). Trabecular carcinoid tumors are composed of long wavy trabeculae and one or two cell layers and are surrounded by dense fibrous connective tissue stroma (1). Mucinous carcinoid tumors are composed of small glands or acini with narrow lumens and are lined by uniform columnar or cuboidal epithelium, and cells contain small round or oval nuclei or have the appearance of goblet cells distended with mucin (1). Strumal carcinoids are composed of thyroid follicles, which contain colloid that has merged with cords of neoplastic cells in dense fibrous stroma, similar to trabecular carcinoid (1). Imaging Features. The imaging features of malignant ovarian carcinoid tumors include a multilocular cystic mass with a soft-tissue component (Fig 26). The mass has low signal intensity on T2-weighted MR images and intermediate signal intensity on T1-weighted MR images. The solid component may appear as a sponge-like mass, and it typically enhances after administration of intravenous contrast material (78). Differential Diagnosis of OMGCTs Some OMGCTs have characteristic features that allow a diagnosis to be confidently made. In particular, the presence of fat within a solid tumor is characteristic of an ovarian teratoma, including immature teratoma, a mixed germ cell tumor with immature elements, and malignant degeneration of a mature cystic teratoma. Other OMGCTs have nonspecific features, making it difficult to establish a diagnosis. However, the imaging features of the tumor, the patient s age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Dysgerminomas, the most common OMGCT, should be differentiated from other purely solid ovarian masses, such as fibrothecomas, Brenner tumors, granulosa cell tumors, and, occasionally, epithelial ovarian and metastatic carcinomas (79). Usually, dysgerminomas manifest in adolescence and early adulthood as a large purely solid tumor with lobules that are separated by fibrous septa that enhance after administration of contrast material. Fibrothecoma, a sex cord stromal tumor, is the most common solid benign ovarian tumor and has predominantly low signal intensity on T2-weighted MR images and intermediate signal intensity on T1-weighted MR images. Granulosa cell tumors

18 794 May-June 2014 radiographics.rsna.org Figure 26. Primary ovarian carcinoid in a 31-year-old woman with carcinoid syndrome. Axial (a, b) and coronal (c) contrast-enhanced CT images show a mixed solid and cystic mass (black arrows) with septal calcifications (white arrow in b) in the left ovary. Histologic analysis revealed a mucinous (ie, goblet cell) carcinoid. are also categorized as sex cord stromal tumors. There are two subtypes of granulosa cell tumors: adult and juvenile. The adult type accounts for 95% of cases of granulosa cell tumors and often occurs in postmenopausal women. Often, it is seen as a multilocular cystic or mixed solid and cystic mass, but it may be purely solid on occasion. Extensive intratumoral hemorrhage is often seen at MR imaging. In addition, granulosa cell tumors are the most common estrogenic ovarian tumors and are associated with uterine enlargement; endometrial hyperplasia may be seen on T2-weighted MR images. Brenner tumors predominantly occur in women who are years old and are characterized by an abundance of fibrous content that demonstrates extensive low signal intensity on T2-weighted MR images. Brenner tumors are reported to have lower signal intensity on T2-weighted images than other solid tumors. Serous epithelial ovarian carcinomas may be predominantly solid and usually have intermediate to high signal intensity on T2-weighted images, often with irregular contours and an infiltrative growth pattern, unlike dysgerminomas, which have a smooth contour. Other OMGCTs such as yolk sac tumors, mixed germ cell tumors without teratomatous elements, and primary ovarian choriocarcinomas usually manifest as a mixed solid and cystic mass, making differentiation from the more common malignant epithelial neoplasms difficult on the basis of imaging findings alone. However, the presence of one of these tumors in a younger patient with the characteristic tumor markers makes it possible to establish a preoperative diagnosis. Tumor Spread and Radiologic Staging There are two staging systems for OMGCTs: the tumor, node, metastasis (TNM) system and the more commonly used surgical system of the

19 RG Volume 34 Number 3 Shaaban et al 795 Table 4: FIGO Staging of Ovarian Tumors Stage I Ia Ib Ic II IIa IIb IIc III IIIa IIIb IIIc IV Description Growth limited to the ovaries Growth limited to one ovary; no ascites with malignant cells; no tumor on external surface of the ovary; capsule intact Growth limited to both ovaries; no ascites with malignant cells; no tumor on external surface of the ovary; capsule intact Stage Ia or Ib tumor with tumor present on the surface of one or both ovaries, ruptured capsule, ascites with malignant cells, or positive peritoneal washings Growth involving one or both ovaries with pelvic extension Extension or metastases to the uterus or fallopian tubes Extension to other pelvic tissues Stage IIa or IIb tumor with tumor present on the surface of one or both ovaries, ruptured capsule, ascites with malignant cells, or positive peritoneal washings Involvement of one or both ovaries with histologically confirmed peritoneal implants outside the pelvis or positive regional lymph nodes; superficial liver metastases; tumor limited to the true pelvis but histologically proved malignant extension to small bowel or omentum Tumor grossly limited to the true pelvis with negative lymph nodes and histologically confirmed microscopic seeding of abdominal peritoneal surfaces or extension to the small bowel or mesentery Tumor in one or both ovaries with histologically confirmed implants; peritoneal metastasis 2 cm to abdominal peritoneal surfaces; negative lymph nodes Peritoneal metastasis >2 cm beyond the pelvis or positive regional lymph nodes Tumor in one or both ovaries with distant metastases; parenchymal liver metastasis; pleural effusion, if present, must be cytologically positive Note. Adapted, with permission, from reference 80. International Federation of Obstetrics and Gynecology (FIGO) (Table 4) (80). Both systems incorporate the most common patterns of tumor spread, including direct invasion of surrounding pelvic structures and extension beyond the pelvis by way of intraperitoneal, lymphatic, or hematogenous dissemination. Although OMGCTs are surgically staged, preoperative imaging may be used to identify local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Unlike epithelial ovarian cancer in which intraperitoneal dissemination is the most common mode of spread, and approximately 70% of patients have peritoneal metastases at staging laparotomy lymphatic spread is the most common mode of spread among OMGCTs (1,81). Dysgerminomas spread late and do so primarily through the lymphatic system. Tumor rupture may cause spillage of tumor contents and extensive peritoneal implantation. Yolk sac tumors are highly malignant and often invade surrounding structures, with extensive spread within the abdominal cavity. Both yolk sac tumors and embryonal carcinomas metastasize early, primarily through the lymphatic system. Immature cystic teratomas spread by implantation throughout the peritoneal cavity and primarily metastasize through the lymphatic system. Choriocarcinomas are highly malignant and locally invasive, spread extensively throughout the abdominal cavity, and metastasize early (39). Local Spread Direct invasion in the pelvis most commonly involves the fallopian tubes, uterus, and contralateral adnexa. With the exception of dysgerminomas, which are bilateral in 6.5% 10% of patients, most OMGCTs are unilateral, a unique feature that makes fertility-sparing surgery possible in this young patient population (8,82). In more advanced disease, the tumor extends to the urinary bladder, rectum, and pelvic sidewall. Findings that indicate invasion of adjacent structures include a loss of intervening fat planes with irregularity of the tumor-organ interface or frank invasion. Pelvic sidewall invasion is characterized by the presence of tumor within 3 mm of muscle, bone, or blood vessels and frank invasion or encasement of these structures (81). Peritoneal Spread Intraperitoneal seeding is a common pattern of spread in ovarian cancer, and OMGCTs are no exception. In OMGCTs, tumor cells slough off into the peritoneal cavity in the pelvis and dependently implant in the cul-de-sac and pelvic organs. From the pelvis, the normal flow of peritoneal fluid carries tumor cells along the right paracolic gutter to the right upper quadrant,

20 796 May-June 2014 radiographics.rsna.org Figure 27. Ovarian dysgerminoma with paraaortic lymph node metastases in a 17-year-old girl. (a) Axial contrast-enhanced CT image shows a predominantly solid mass (arrows) in the left ovary. (b) Axial contrastenhanced CT image shows enlargement of a left paraaortic lymph node (arrow). where implants deposit on the liver capsule and diaphragmatic surface (81). Invasion and occlusion of diaphragmatic lymphatics obstruct resorption of peritoneal fluid, resulting in ascites and enlargement of pericardiophrenic lymph nodes (81). Thus, pericardiophrenic lymphadenopathy and ascites should always prompt a meticulous search for peritoneal metastases. Tumor implants in the peritoneal cavity are most commonly seen in the cul de sac, paracolic gutters, omentum, subphrenic space, or mesentery. Omental metastases may be too small to see at imaging; when they are visible, they appear as areas of fine nodular stranding or thickened soft issue referred to as omental cake. Mesenteric implants may distort and obstruct the bowel by inciting adhesions or by frank invasion (81). Lymphatic Spread Lymph node metastases are a poor prognostic indicator, with a prevalence of 18% among all subtypes of OMGCTs. Dysgerminomas have the highest propensity for metastatic adenopathy, which is present in 28% of dysgerminomas, followed by mixed germ cell tumors, with metastatic adenopathy present in 16% of tumors, and immature teratomas, with metastatic adenopathy present in 8% of tumors (83). The three routes of lymphatic drainage of the ovary are along the ovarian veins, broad ligament, and round ligament (81). The main route is along the ovarian veins to the paraaortic and paracaval lymph nodes (Fig 27). The lymphatics also drain along the broad ligament to the internal and external iliac lymph nodes and to the junctional nodes at the junction between Figure 28. Liver metastases in a 27-year-old woman with a yolk sac tumor. Contrast-enhanced CT image shows multiple parenchymal metastases (arrows) in the liver. True parenchymal metastases are less defined than capsular implants and are surrounded by liver parenchyma. the internal and external iliac nodal groups. The third route of drainage is along the round ligament to the inguinal lymph nodes. Distant Metastases Hematogenous metastases are rare at the time of initial presentation; however, they may be seen in the liver and lungs in patients with recurrent disease. Metastases to the brain, bones, adrenal glands, and other abdominal organs are far less common (81). Stage IV disease is characterized by distant metastases. The most common

21 RG Volume 34 Number 3 Shaaban et al 797 Figure 29. Ovarian immature teratoma with peritoneal metastases in a 27-year-old woman. Axial (a, b) and coronal (c) contrastenhanced CT images show a mixed solid and cystic mass (* in a) with focal calcifications in the left ovary and a large peritoneal metastatic mass in the right lower quadrant (white arrow in c). A large calcified capsular hepatic mass (black arrows in b and c) with a smooth, welldefined interface with the liver parenchyma is also seen. Note the peripheral location and biconvex shape of the mass. finding of distant metastases in patients with OMGCT is a malignant pleural effusion, which must be confirmed at thoracentesis and cytologic analysis, although the presence of pleural thickening, nodularity, or masses makes malignancy likely (81). Hepatic parenchymal disease (stage IV) must be distinguished from capsular metastases (stage III). True parenchymal metastases are ill defined and surrounded by hepatic parenchyma, whereas capsular implants are well-defined, biconvex, and peripherally located (Figs 28, 29) (81). Capsular implants located along the falciform ligament may be confused with parenchymal metastases; however, their typical location and smooth margins may help confirm the peritoneal location. Treatment Surgery The staging and classification of OMGCTs largely parallel those for epithelial ovarian neoplasms. Traditionally, comprehensive surgical staging included a vertical midline incision with hysterectomy, bilateral salpingo-oophorectomy, omentectomy, collection of ascites or cytologic washings, peritoneal biopsies, retroperitoneal and pelvic lymphadenectomy, and diaphragm biopsy (82). However, evidence suggests that a more limited procedure that includes laparotomy, tumor resection, and careful peritoneal and lymph node examination may suffice (82,84). In this approach, unilateral salpingo-oophorectomy is performed, and the uterus and contralateral ovary, if uninvolved, are left in place to maintain fertility. Biopsy of the contralateral ovary is only performed if an abnormality is encountered; otherwise, it is left undisturbed to decrease the risk for infertility from adhesions or ovarian failure (8). All peritoneal surfaces and the diaphragm and omentum are examined, and any abnormalities are resected or biopsied. Retroperitoneal and ipsilateral pelvic lymph nodes are palpated and removed only if an abnormality is detected, and ascites and peritoneal washings are collected before any manipulation of the involved ovary is performed. In patients with advanced-stage disease, all easily accessible tumor is removed. The degree of tumor debulking is tempered by the knowledge that most OMGCTs have excellent chemosensitivity: The less aggressive fertility-sparing approach is supported by the highly chemosensitive nature of the tumors, low incidence of bilateral ovarian disease, and lack of apparent survival benefit in patients with inadequately staged tumors (82).