Radiological-pathological correlation of yolk sac tumor in 20 patients.

XML Template (2014) [8.12.2014–11:25am] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140212/APPFile/SG-ACRJ140212.3d

(ACR)

[1–9] [PREPRINTER stage]

Acta Radiol OnlineFirst, published on December 9, 2014 as doi:10.1177/0284185114561916

Original Article

Radiological–pathological correlation of yolk sac tumor in 20 patients

Acta Radiologica 0(0) 1–9 ! The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0284185114561916 acr.sagepub.com

YangKang Li1, Yu Zheng2, JianBang Lin1, GuiXiao Xu3, AiQun Cai1, RuoWei Chen4 and MingYao Wu5

Abstract Background: Yolk sac tumor (YST) is a rare tumor. Familiarity of its radiological characteristics may permit preoperative diagnosis and improve surgical management of patients. However, a detailed description of the imaging features of YST with pathological correlation in particular is scarce. Purpose: To investigate computed tomography (CT) findings of YSTs with pathological correlation. Material and Methods: CT images of 20 patients with pathologically proven YST were retrospectively reviewed. The location, size, margin, internal architecture, and pattern and degree enhancement of the lesion were evaluated. Radiological findings were correlated with pathological results. Results: The locations of 20 tumors were distributed between the testis (n ¼ 3), ovary (n ¼ 6), sacrococcygeal area (n ¼ 6), rectum (n ¼ 1), and mediastinum (n ¼ 4). The median age was 13 years. On CT images, all tumors were seen as oval (n ¼ 14) or irregular (n ¼ 6), well-defined (n ¼ 16) or ill-defined (n ¼ 4) masses with a mean size of 9.7 cm. The lesions were solid cystic (n ¼ 10), entirely solid (n ¼ 6), or predominantly cystic (n ¼ 4). Intratumoral hemorrhage, calcification, and fatty tissue were seen in nine, three, and two tumors, respectively. Discontinuity of the tumor wall was seen in eight tumors. After contrast media administration, most tumors showed heterogeneous moderate to marked enhancement (n ¼ 7) or heterogeneous marked enhancement (n ¼ 9). Enlarged intratumoral vessels were seen in 17 tumors. Conclusion: YST usually appears as a large solid-cystic mass with intratumoral hemorrhage, capsular tear, marked heterogeneous enhancement, and enlarged intratumoral vessels on CT images. Intratumoral calcification and fatty tissue, although rare, may indicate a mixed YST containing teratoma component.

Keywords Yolk sac tumor, radiology, computed tomography (CT), pathology Date received: 1 August 2014; accepted: 7 November 2014

Introduction Yolk sac tumor (YST) is a primitive malignant germ cell tumor (GCT) and is uncommon in clinical practice. It usually occurs in the mid-line of the body involving gonadal and extragonadal organs and is often seen in children and young adults (1). This kind of tumor is histopathologically characterized by the presence of Schiller-Duval bodies. Up to now, the combination of operation with chemotherapy remains the mainstay of therapy for YST (2). So familiarity of its radiological characteristics may permit preoperative diagnosis and improve surgical management of patients. It can aid in surgical planning, and may help distinguish benign

1 Department of Radiology, Cancer Hospital, Shantou University Medical College, Shantou, PR China 2 Department of Clinical Pharmacology, Cancer Hospital, Shantou University Medical College, Shantou, PR China 3 State Key Laboratory of Oncology in South China, Department of Diagnostic Imaging and Intervening Center, Cancer Center of Sun Yat-sen University, Guangzhou, PR China 4 Department of Diagnostic Imaging, the Second affiliated Hospital of Shantou University Medical College, Shantou, PR China 5 Department of Pathology, Shantou University Medical College, Shantou, PR China

Corresponding author: YangKang Li, Department of Radiology, Cancer Hospital, Shantou University Medical College, No 7 Raoping Rd, Shantou, Guangdong Province 515041, PR China. Email: [email protected]

Downloaded from acr.sagepub.com at CHINESE UNIV HONG KONG LIB on October 6, 2015


(ACR)


2

Acta Radiologica 0(0)

from malignant tumors and thus avoid inappropriate management, or enable the surgeon to anticipate this type of tumor preoperatively so that adequate procedures can be planned. Some clinicopathological studies of YST have been reported (3–6). To our knowledge, however, only a few reports concerning the imaging characteristics of YST have been published (7–10). Furthermore, these studies were case reports or conducted on this tumor only targeting one original site. A detailed description of the imaging features of YST with pathological correlation in particular is scarce. The present study describes the computed tomography (CT) appearances of 20 patients with YST correlated with pathological findings, with the aim to be familiar with the imaging appearances of this entity and improve the accuracy of preoperative diagnosis.

Material and Methods This retrospective study was approved by the institutional review board. The need for informed consent was waived. Between August 2006 and March 2014, 20 patients (11 boys/men, 9 girls/women) with pathological proven YSTs were identified. A total of 20 tumors distributing in testis (n ¼ 3), ovary (n ¼ 6), sacrococcygeal region (n ¼ 6), rectum (n ¼ 1), and anterior mediastinum (n ¼ 4) was evaluated. CT examinations of two patients were performed on a PQ5000 spiral CT scanner (Picker, New York, NY, USA). Nine patients were examined using a Philips Brilliance TM 16-detector-row scanner (Philips Medical Systems, Cleveland, OH, USA), six patients were examined using a GE Brightspeed Elite 16-detector-row scanner, and three patients were examined using a GE Lightspeed VCT 64-detector-row scanner (GE Healthcare, Milwaukee, WI, USA). After a series of unenhanced sections, all patients received intravenous bolus injection of contrast medium (Ultravist 300; Bayer Schering Pharma, Berlin-Wedding, Germany) at a rate of 1–3 mL/s and a volume of 15–90 mL. For the PQ5000 scanner, the section thickness of unenhanced and enhanced images was 10 mm. For three multidetector CT (MDCT) scanners, the section thickness of unenhanced and enhanced images was 5 mm and the reconstruction interval was 1.25 mm. The CT images were reviewed independently by two radiologists who specialized in oncological imaging. Their interpretations were arrived at by consensus. The following CT features of each mass were assessed: tumor size (maximal diameter), shape (oval or irregular), margin (well-defined or ill-defined), density (entirely solid, predominantly cystic, or solid cystic), internal component (presence of hemorrhage, necrosis, calcifications, or fatty tissue), integrity of the tumor wall, and pattern of enhancement (homogeneous or

heterogeneous). The degree of enhancement was subjectively assessed and categorized as follows: mild, when the enhancement was similar to that of adjacent muscle; moderate, when the enhancement was higher than that of muscle, but lower than that of blood vessels; and marked, when the enhancement was approaching that of blood vessels. After review of the radiologic studies, surgical notes and excised specimens were correlated with radiological findings.

Results Clinical findings The median age of diagnosis was 13 years (age range, 1–31 years). The level of serum alpha-fetoprotein (AFP) of all cases was over 1000 ng/mL (normal value, 7 ng/mL). Nineteen cases received surgical treatment and cisplatin-based chemotherapy. One case with rectal YST received fine needle biopsy and proctoscope examination. Proctoscopy showed a mass protruding from the anterior rectal wall with intact overlying mucosa. This patient refused treatment and left hospital.

CT manifestations The size of the tumors was in the range of 3.0–24.0 cm (mean, 9.7 cm). The shape was seen as oval (n ¼ 14) or irregular (n ¼ 6). Sixteen tumors showed a well-defined margin, and four tumors showed an ill-defined contour. Six tumors showed a completely solid mass (Figs. 1 and 2). Four tumors showed a predominantly cystic mass (Fig. 3). A mixed solid and cystic nature was seen in 10 tumors (Figs. 4 and 5). On unenhanced CT images, the density of the solid component of all tumors was 31–49 HU (mean, 37 HU) which was

Fig. 1. A 2-year-old boy with testicular YST. Contrast-enhanced CT scan shows a well-circumscribed, oval solid mass with enlarged intratumoral vessel (white arrow).



(ACR)


Li et al.

3

Fig. 2. A 25-year-old man with rectal YST. Contrast-enhanced CT scan shows an entirely solid mass originating from the anterior rectal wall. Heterogeneous moderate to marked enhancement of the tumor and enlarged intratumoral vessels are detected (black arrow).

similar to that of muscle. Intratumoral hemorrhage, which was defined as an amorphous hyperdense lesion with a relatively lower attenuation compared with calcification on non-contrast CT scans and no enhancement on contrast-enhanced CT scans, was seen in nine tumors (Fig. 3a and b). Flecks of intratumoral calcification were seen in three tumors (Figs. 3d and 4a). Fatty tissue was seen in two tumors (Figs. 3d and 4a). Discontinuity of the tumor wall was seen in eight tumors (Figs. 3c and 4a). After contrast medium administration, there was heterogeneous mild to moderate enhancement in four, heterogeneous moderate to marked enhancement in seven, and heterogeneous marked enhancement in nine at the solid portion of the lesions. Moreover, intratumoral enlarged vessels were seen in 17 tumors (Figs. 1, 2, 3c, and 5a). CT findings of all tumors are summarized in Table 1.

Surgical and pathological results All ovarian, testicular, and sacrococcygeal tumors as well as one mediastinal tumor were completely removed surgically. Incomplete excision was performed on two mediastinal tumors due to extensive invasion of adjacent major vasculatures. At gross evaluation, the tumors that were completely removed were encapsulated with a smooth, glistening external surface. Capsular tear was detected in 13 tumors. Characteristically, the masses were cystic and solid with soft, gray-to-yellow tissue as well as areas of hemorrhage and necrosis on the cut sections. Under light microscope, all tumors had varying degrees of hemorrhage, necrosis or cystic degeneration with multiple enlarged vessels (Fig. 3e and f). The tumors displayed a variety of histological patterns in different cases or at different areas of the same case. Specifically, the reticular pattern was seen in all

tumors. The endodermal sinus pattern and SchillerDuval body were seen in 16 tumors (Fig. 5b and c). The papillary pattern was seen in nine tumors. The glandular-alveolar pattern was seen in seven tumors. The hepatoid and polyvesicular vitelline patterns were seen in two tumors, respectively. The solid pattern was seen in one tumor. The eosinophilic and PAS-positive hyaline globule was seen in 15 tumors. Pure YST was found in 11 patients. Mixed YST was found in one child patient and seven young adult patients. Specifically, cystic teratoma component was found in four tumors, including one sacrococcygeal tumor and three ovarian tumors (Fig. 4b). Malignant teratoma, embryonal carcinoma, or carcinoid component was found in three mediastinal tumors (Fig. 5d). Choriocarcinoma component was found in one ovarian tumor. The patient with rectal YST only accepted fine needle biopsy and the histological type of the tumor was unable to be determined due to the limited pathological tissues.

Discussion In the present study, the CT findings of YST ranged from entirely solid to predominantly cystic or presented as heterogeneous appearances consisting of a mixed solid and cystic nature. Most of the tumors were oval with well-defined margins, which may be associated with the origin of this kind of tumor. YSTs originate in germ cells not in the epithelium. Unlike YSTs, epithelial malignant neoplasms usually infiltrate, rather than cause mass effect on surrounding structures; the shape is usually irregular and the margin is often unclear. YSTs tend to grow in an expansive centripetal fashion with compression of adjacent organs. In our series, most tumors were large in size (>5 cm) and the mean maximal diameter of all tumors reached 9.7 cm. On unenhanced CT, the solid portion of YSTs appeared as isodense with normal muscle as the standard for comparison. A pattern of heterogeneous moderate to marked enhancement or heterogeneous marked enhancement was more common and was present in 80% of tumors (16/20). Heterogeneity corresponds to intralesional hemorrhage, necrosis, or cystic change. Obvious enhancement reveals rich blood supply of the tumor parenchyma. Both were confirmed on cut sections and microscopic examinations. Intralesional hemorrhage may be caused by the hypervascularity of the tumor. Moreover, large tumor size may outgrow tumor blood supply and also cause intratumoral hemorrhage, necrosis or cystic degeneration. Awareness of intratumoral hemorrhage is recommended because it is difficult to identify in some cases. In the present study, precontrast CT only showed evidence of hemorrhage in nine tumors, but pathological findings revealed



(ACR)


4


Fig. 3. A 16-year-old girl with ovarian YST. (a) Precontrast CT scan shows a high density lesion within a cystic mass (black arrow). (b) This high density lesion has no enhancement on postcontrast CT image, which indicates the lesion is hemorrhage (black arrow). (c) Contrast-enhanced CT scan shows a predominantly cystic mass with peritoneal metastasis and massive ascites in the abdomen. Heterogeneous marked enhancement of the tumor and enlarged intratumoral vessels are detected (black arrow). Discontinuity of the tumor wall is seen (white arrow). (d) The mass contains a small amount of calcification and fatty tissue (black arrow) which represent the pathologically proven mature teratoma component. Another peritoneal metastasis with heterogeneous marked enhancement is seen (white arrow). (e, f) Photomicrographs (HE 200) show massive hemorrhage (black arrow) and abundant dilated vessels (white arrow) that correspond to the imaging appearances.



(ACR)


Li et al.

5

Fig. 4. A 2-year-old boy with sacrococcygeal YST. (a) Contrast-enhanced CT scan shows an irregular solid-cystic mass with disruption of the tumor wall and invasion of gluteus maximus. The mass contains calcification (black arrow) and fatty tissue (white arrow) which represent the pathologically proven mature teratoma component. (b) Photomicrograph (HE 400) shows a cystic teratoma component containing calcification (white arrow) and fatty tissue (black arrow) that correspond to the imaging findings in Figs 3d and 4a.

Fig. 5. A 31-year-old man with anterior mediastinal YST. (a) Contrast-enhanced CT scan shows a huge solid-cystic mass with heterogeneous mild to moderate enhancement. Enlarged vessels are seen in the mass (black arrow). The mass encases adjacent major vessels. Obstruction of the superior vena cava is detected (white arrow). (b) Most distinctive pathological feature of YST is the Schiller-Duval body (HE 400). (c) Photomicrograph shows an atypical Schiller-Duval body (black arrow) with immature neural tissue (white arrow), indicating the transition from YST to malignant teratoma tissue (HE 400). (d) A malignant teratoma component containing immature neuroepithelial tissue (white arrow) is found in the tumor (HE 400).


Ovary

Ovary Ovary

Ovary

Ovary

SC region SC region

SC region

SC region

SC region

SC region

Rectum

Mediastinum

6/F/15 7/F/20

8/F/14

9/F/17

10/F/1 11/M/2

12/F/2

13/F/1

14/M/2

15/F/5

16/M/25

17/M/20

Testis

3/M/24

5/F/16

Testis

2/M/1

Ovary

Testis

1/M/2

4/F/19

Tumor location

Case no./ Sex/Age (years)


YST þembryonal carcinoma

7.0

9.5

9.0

5.0

7.0

6.5

5.5 4.0

15.0

Irregular

Oval

Oval

Irregular

Irregular

Oval

Oval Irregular

Oval

Oval

Well-defined

Ill-defined, tumor wall discontinuous Well-defined, tumor wall discontinuous Well-defined

Well-defined

Well-defined, tumor wall discontinuous Well-defined Ill-defined, tumor wall discontinuous Well-defined

Well-defined Well-defined, tumor wall discontinuous Well-defined

Well-defined, tumor wall discontinuous

Well-defined

Well-defined

Well-defined

Well-defined

Margin

Solid cystic, fat, calcification Predominantly cystic, hemorrhage, calcification Entirely solid, hemorrhage Entirely solid

Entirely solid

Predominantly cystic, hemorrhage Solid cystic, hemorrhage Solid cystic Solid cystic, hemorrhage Entirely solid

Predominantly cystic, hemorrhage, fat and calcification Solid cystic Solid cystic, hemorrhage

Solid cystic

Solid cystic

Entirely solid

Entirely solid

CT plain scan

Heterogeneous/ moderate to marked Heterogeneous/ moderate to marked

Heterogeneous/marked Heterogeneous/ mild to moderate Heterogeneous/ moderate to marked Heterogeneous/ moderate to marked Heterogeneous/ mild to moderate Heterogeneous/marked

Heterogeneous/marked

Heterogeneous/marked

Heterogeneous/marked Heterogeneous/marked

Heterogeneous/ mild to moderate Heterogeneous/ moderate to marked Heterogeneous/ moderate to marked Heterogeneous/ moderate to marked Heterogeneous/marked

Enhancement pattern/ degree

Yes

yes

Yes

Yes

Yes

Yes

Yes No

Yes

Yes

Yes Yes

Yes

Yes

Yes

No

Yes

(continued)

Dilated vessel in the mass

6

Unknown

YST þ cystic teratoma Pure

Pure

Pure

YST þ choriocarcinoma Pure Pure

17.5

Oval Oval

Irregular

20.0

6.5 24.0

Irregular

Oval

Oval

Oval

Shape

13.0

6.0

3.0

4.5

Diameter (max, cm)

(ACR)

Pure YST þ cystic teratoma Pure

YST þ cystic teratoma YST þ cystic teratoma

Pure

Pure

Pure

Histology

Table 1. CT findings of 20 patients with YSTs.

XML Template (2014) [8.12.2014–11:25am] //blrnas3.glyph.com/cenpro/ApplicationFiles/Journals/SAGE/3B2/ACRJ/Vol00000/140212/APPFile/SG-ACRJ140212.3d [1–9] [PREPRINTER stage]



(ACR)


No Yes

Heterogeneous/ mild to moderate Heterogeneous/marked Heterogeneous/marked Solid cystic, hemorrhage Predominantly cystic Solid cystic, hemorrhage 8.0 9.5

Oval Oval

Ill-defined, tumor wall discontinuous Well-defined Ill-defined, tumor wall discontinuous Oval 14.0

Mediastinum Mediastinum 19/M/19 20/M/25

SC region, sacrococcygeal region.

Mediastinum 18/M/31

YST þ malignant teratoma Pure YST þembryonal carcinoma þ carcinoid

Enhancement pattern/ degree CT plain scan Margin Shape Diameter (max, cm) Histology Tumor location Case no./ Sex/Age (years)

Table 1. Continued.

Yes

7 Dilated vessel in the mass

Li et al.

hemorrhage in all tumors. In our opinion, non-contrast CT examination is useful to demonstrate hyperdensity material that probably indicates active intratumoral hemorrhagic content. But CT has limitation to detect subacute and chronic hemorrhage or small areas of hemorrhage. Furthermore, differentiation necrosis or cystic changes within tumors from liquefied hemorrhage is also difficult. Magnetic resonance imaging (MRI) can provide complementary information regarding intratumoral hemorrhage, especially in the subacute and chronic stages (11). Yamaoka et al. (12) reported that three of four (75%) YSTs had intratumoral hemorrhage which showed high intensity on T1-weighted MR images. On CT images, discontinuity or disruption of the tumor wall was seen in eight tumors. This sign was described as capsular tear or rupture on gross pathology (13). If the capsule is disrupted, the tumor component may rupture into the adjacent structures, such as abdominopelvic cavity, surrounding soft tissue space, pleural cavity, lung parenchyma, or tracheobronchial tree, causing inflammation, adhesion, implantation metastasis, or invasion and encasement of adjacent organs. In our opinion, tumor enlargement may result in ischemia, necrosis, and then rupture. Infection also has been suggested as a cause of capsular tear or rupture. Some authors have proposed that sebaceous materials or digestive enzymes derived from tumor tissue cause inflammation and necrosis, which can result in capsular tear (14–16). In our study, capsular tear was found in 13 tumors by pathological study. It may indicate that CT has limitation to detect slight tear of tumor capsule. In our study, intratumoral vessels were detected in 85% of the tumors (17/20). This finding was consistent to previous studies. Choi et al. (10) reported that massive intratumoral vessels were observed in all 10 cases on postcontrast CT images and especially used the term ‘‘bright dot sign’’ to depict this CT finding. Yomaoka et al. (12) also reported that tumors showed a signal void on MR images and noted the presence of abundant vessels within tumors. Intralesional vessels of YSTs usually have dilated lumen and marked enhancement. This classical imaging finding is considered to be a result of increased vascularity and the formation of small vascular aneurysms in the tumor (13). In this study, we reported one rectal YST which had an exophytic growth pattern with the epicenter located well outside the anterior wall of rectum. It could be the second case of rectal YST in literature and the first one was reported in 2000 (17). In male patients, tumors arising from the anterior rectal wall with exophytic growth pattern can even mimic tumors of prostatic origin on axial CT images. Thus, the classic rule regarding determination of the organ of origin based on the



(ACR)


8


location of the epicenter of a tumor is often not applicable. In such cases, the recognition of the normal prostate is a valuable clue in excluding the possibility of prostatic tumors. Moreover, tumor-rectal wall continuity is detected on CT images, which can suggest the diagnosis of a rectal mass. Although calcification and fatty tissue were not common clinicopathological features of YST, they have been reported in previous studies (7,8). Most calcifications within YSTs are circumscribed and welldefined. In our study, one of the three calcified tumors showed simple calcification and the other two showed calcification with fat. A teratoma component was considered to be contained in these tumors, which was confirmed in the last two cases by pathological results. In teratoma, calcifications may represent teeth, but they more commonly are fragments of calcified cartilage or bone (8). In our opinion, simple calcification of the first case may originate from previous episodes of hemorrhage or tumor necrosis with cystic degeneration. On pathology, Schiller-Duval body is a distinguishing feature of YST and is most often found in association with the endodermal sinus pattern. It is characterized by solitary papillary structure with central vessel within its connective tissue core projecting into a luminal space. Another frequently encountered pathological feature of YST is hyaline globules, which are eosinophilic, PAS-positive, diastase-resistant globules. However, YST can be difficult to diagnose pathologically because they exhibit a wide variety of histologic patterns and multiple patterns are typically present in an individual tumor. The review of pathology in our patients showed that the two most common patterns were reticular pattern (also called microcystic pattern) and the endodermal sinus pattern, in agreement with the pathological literature (18). The reticular growth pattern of tumor cells formed microcystic or glandular structures, which contributed to the cystic or necrotic changes seen on the CT images (19). In contrast to adult YSTs which are often found in combination with other kinds of germ cell tumor, infant and young children YSTs often present as a pure tumor (20). In this study, there was an obviously uneven distribution of mixed YSTs with an adult: children ratio of 7:1, in accordance with the literature reports. Presence of any admixed malignant GCT component in the primary will make the efficacy of treatment become indefinite (18,21). It suggests that this mixed malignant tissue may continue to grow even as the tumor marker normalizes after chemotherapy (22). In our opinion, the existence of calcification with fatty tissue detected by imaging modalities may indicate the tumor containing teratoma component. However, attempts to predict the existence and potential high-risk behavior of

any admixed malignant component in YSTs from their imaging features is difficult, because they often lack characteristic imaging findings. YST usually occurs in children and young adults (23). In our series, the age of all patients was in the range of 1–31 years (mean age, 13 years). In this period, germ cell tumors are the most common histological type of tumor. Most of them are benign teratomas. But malignant germ cell tumors may be encountered. Among malignant germ cell tumors, immature teratoma is the most common and is followed by dysgerminoma and YST (24). Imaging findings described for immature teratomas are predominantly cystic or solid cystic tumors and almost always contain fatty tissue (25,26). Dysgerminomas usually appear as a predominantly solid tumor without necrosis and hemorrhage (27). They are often associated with intratumoral fibrovascular septa, which show prominent enhancement. These imaging findings are different from those obtained in YSTs. Moreover, dilated intratumoral vessels on postcontrast CT images were also absent in immature teratoma or dysgerminoma. In the present study, different CT equipments and techniques were used. However, this problem is simply unavoidable due to the rarity of this type of tumor, and should not have significantly affected the imaging characteristics studied. In conclusion, we present the largest cohort of radiological studies of YSTs to date. They normally occur in children and young adults and are often seen as large, well-defined, solid-cystic masses with intratumoral hemorrhage, capsular tear, marked heterogeneous enhancement, and enlarged intratumoral vessels on CT images. Intratumoral calcification and fatty tissue, although rare, may indicate a mixed YST containing teratoma component. Conflict of interest None declared.

Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References 1. Talerman A, Haije WG, Baggerman L. Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP. Cancer 1980;46:380–385. 2. Taskinen S, Fagerholm R, Aronniemi J, et al. Testicular tumors in children and adolescents. J Pediatr Urol 2008;4: 134–137.



(ACR)


Li et al.

9

3. Kurman RJ, Norris HJ. Endodermal sinus tumor of the ovary: a clinical and pathologic analysis of 71 cases. Cancer 1976;38:2404–2419. 4. Yoshida M, Matsuoka K, Nakazawa A, et al. Sacrococcygeal yolk sac tumor developing after teratoma: a clinicopathological study of pediatric sacrococcygeal germ cell tumors and a proposal of the pathogenesis of sacrococcygeal yolk sac tumors. J Pediatr Surg 2013;48:776–781. 5. Kao CS, Idrees MT, Young RH, et al. Solid pattern yolk sac tumor: a morphologic and immunohistochemical study of 52 cases. Am J Surg Pathol 2012;36: 360–367. 6. Young RH, Ulbright TM, Policarpio-Nicolas ML. Yolk sac tumor with a prominent polyvesicular vitelline pattern: a report of three cases. Am J Surg Pathol 2013;37: 393–398. 7. Sham JS, Chan FL, Lau WH, et al. Primary mediastinal endodermal sinus tumors: CT evaluation. Clin Imaging 1989;13:299–304. 8. Brammer HM 3rd, Buck JL, Hayes WS, et al. From the archives of the AFIP. Malignant germ cell tumors of the ovary: radiologic-pathologic correlation. Radiographics 1990;10:715–724. 9. Levitin A, Haller KD, Cohen HL, et al. Endodermal sinus tumor of the ovary: imaging evaluation. Am J Roentgenol 1996;167:791–793. 10. Choi HJ, Moon MH, Kim SH, et al. Yolk sac tumor of the ovary: CT findings. Abdom Imaging 2008;33: 736–739. 11. Teo SY, Babagbemi KT, Peters HE, et al. Primary malignant mixed mullerian tumor of the uterus: findings on sonography, CT, and gadolinium-enhanced MRI. Am J Roentgenol 2008;191:278–283. 12. Yamaoka T, Togashi K, Koyama T, et al. Yolk sac tumor of the ovary: radiologic-pathologic correlation in four cases. J Comput Assist Tomogr 2000;24:605–609. 13. Shaaban AM, Rezvani M, Elsayes KM, et al. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features. Radiographics 2014;34: 777–801. 14. Hiraiwa T, Hayashi T, Kaneda M, et al. Rupture of a benign mediastinal teratoma into the right pleural cavity. Ann Thorac Surg 1991;51:110–112.

15. Ashour M, el-Din Hawass N, Adam KA, et al. Spontaneous intrapleural rupture of mediastinal teratoma. Respir Med 1993;87:69–72. 16. Sjo¨vall K, Nilsson B, Einhorn N. Different types of rupture of the tumor capsule and the impact on survival in early ovarian carcinoma. Int J Gynecol Cancer 1994;4: 333–336. 17. Miller KD, Michael H, Jacobson L, et al. Primary yolk sac tumor of the rectum. Cancer Invest 2000;18:597–601. 18. Zaloudek CJ. Pathology of germ cell tumors. In: Soslow RA, Tornos C (eds) Diagnostic pathology of ovarian tumors. New York: Springer, 2011, pp.155–192. 19. Zhang B, Gao S, Chen Y, et al. Primary yolk sac tumor arising in the pancreas with hepatic metastasis: a case report. Korean J Radiol 2010;11:472–475. 20. Vaysse C, Delsol M, Carfagna L, et al. Ovarian germ cell tumors in children. Management, survival and ovarian prognosis. A report of 75 cases. J Pediatr Surg 2010;45: 1484–1490. 21. Nawa A, Obata N, Kikkawa F, et al. Prognostic factors of patients with yolk sac tumors of the ovary. Am J Obstet Gynecol 2001;184:1182–1188. 22. Syed AA, Lynch VP. Mediastinal endodermal sinus tumour: surgical role in chemotherapy resistant cases. J R Coll Surg Edinb 2000;45:199–201. 23. Shah JP, Kumar S, Bryant CS, et al. A population-based analysis of 788 cases of yolk sac tumors: A comparison of males and females. Int J Cancer 2008;123:2671–2675. 24. Smith HO, Berwick M, Verschraegen CF, et al. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol 2006;107:1075–1085. 25. Yamaoka T, Togashi K, Koyama T, et al. Immature teratoma of the ovary: correlation of MR imaging and pathologic findings. Eur Radiol 2003;13:313–319. 26. Takahashi K, Al-Janabi NJ. Computed tomography and magnetic resonance imaging of mediastinal tumors. J Magn Reson Imaging 2010;32:1325–1339. 27. Tanaka YO, Kurosaki Y, Nishida M, et al. Ovarian dysgerminoma: MR and CT appearance. J Comput Assist Tomogr 1994;18:443–448.


Gastric adenocarcinoma with yolk sac tumor differentiation and liver metastasis of yolk sac tumor component.

Primary omental yolk sac tumor.

Ruptured testicular yolk sac tumor.

Alpha-Fetoprotein in yolk sac tumor.

Transformation of seminoma to yolk sac tumor.

Endometrial Yolk Sac Tumor with Omental Metastasis.

Yolk sac tumor of vagina: a case report.

Pure glandular endometrioid-like yolk sac tumor of the testis.

Primary endodermal sinus (yolk sac) tumor of the falciform ligament.

Primary yolk sac tumor of the retroperitoneal region.

Primary Nasopharngeal Yolk Sac Tumor: A Case Report.

Yolk sac carcinoma.

Teratomas and yolk-sac tumours.

[Pathology of the yolk sac: endosonographic results].

Growth of a human yolk sac tumor cell line with yolk sac-derived functions in selenium-supplemented chemically defined synthetic medium.

Yolk Sac Tumor of the Testis in Infants and Children: A Clinicopathologic Analysis of 33 Cases.

Role of neoadjuvant chemotherapy in the management of advanced ovarian yolk sac tumor.

Clinical dilemma in management of yolk sac tumor of childhood testis.

Successful radiotherapy in postoperative recurrence of a primary mediastinal yolk sac tumor: A case report.

Testicular yolk sac tumor of myxomatous, reticular, and polyvesicular vitelline type in a newborn calf.

A Rare Case of Primary Anterior Mediastinal Yolk Sac Tumor in an Elderly Adult Male.

Yolk sac tumor in the abdominal wall of an 18-month-old girl: a case report.

Intracranial pure yolk sac tumor in the anterior third ventricle of an adult: A case report.

[A case of yolk sac tumor originating in the mediastinum (author's transl)].