Review of Ovarian Tumors in Children and Adolescents:

Radiologic- Pathologic Correlation

LEARNING OBJECTIVES

• Discuss the diagnostic workup of children and adolescents with ovarian tumors.

• Describe the clinical and pathologic features of ovarian tumors in children and adolescents.

• List the imaging features of ovarian tumors in children and adolescents.

Introduction

• Ovarian neoplasms are uncommon in the pediatric population, with an estimated incidence of 2.6 cases per 100,000 girls per year.

• Ovarian malignancy comprises aproximately 1%–2% of all childhood malignancies.

• Rare compared with in adults but are the most common genital tumor, accounting for 60%–70% of all gynecologic malignancies in this age group

Clinical Manifestations

• Abdominal pain - most common (57%)

• Palpable abdominal or pelvic mass (46%)

• Nausea, vomiting, poor appetite, weight loss, constipation, and urinary frequency.

• Tenderness may be a symptom of torsion, hemorrhage, or rupture of ovarian tumors.

• Endocrine abnormalities can be the initial manifestation of hormone-producing ovarian tumors (isosexual precocious puberty, including breast enlargement, abnormal vaginal bleeding, and development of pubic and axillary hair)

• Menstrual irregularity - hypermenorrhea or amenorrhea.

• Signs of virilization or masculinization (eg, acne, deepening of the voice, hirsutism, and clitoral enlargement) may be seen in both prepubertal girls and female adolescents.

Diagnostic Workup

• First diagnostic step is to define the exact site of origin and distinguish the lesion from other diseases with similar symptoms (eg, appendicitis).

• Lesions with an ovarian origin should be determined to be either physiologic or neoplastic.

• The likelihood of malignancy should also be assessed because this is critical when assigning patients to either conservative management or an appropriate surgical approach for fertility preservation.

• Transabdominal ultrasonography (US) without the use of an endovaginal probe is the initial imaging modality of choice in children and adolescents.

• US is useful to determine overall tumor size and identify whether an ovarian mass is cystic, solid, or complex.

• CT or MR imaging should be performed to obtain additional information, such as the nature and extent of the tumor.

• Although it often is difficult to distinguish between benign and malignant ovarian tumors, imaging findings can help predict malignancy

• Malignant tumors will appear predominantly solid or heterogeneous and tend to be larger than benign tumors.

• MR imaging is the preferred imaging modality in some cases owing to the excellent soft-tissue contrast it provides. However, the MR imaging examination is longer and may require sedation in a younger child.

• Thus, despite the use of radiation, CT remains an important imaging modality for the staging of ovarian tumors and surgical planning.

• Assay of serum tumor markers is the next step in establishing the differential diagnosis.

• Among these tumor markers, elevated AFP, b-hCG, and CA-125 levels raise concern for ovarian malignancy. However, negative tumor markers do not exclude the possibility of malignancy because the markers are positive in only 54% of cases.

Germ Cell Tumors

• Although GCTs are relatively infrequent and the majority are benign in adult women, GCTs are the most common type of ovarian neoplasm, and one-third of ovarian GCTs are malignant in children and adolescents.

• As defined by the World Health Organization, the histologic subtypes of ovarian GCTs include :– teratoma (mature, immature, or monodermal)– dysgerminoma– yolk sac tumor– embryonal carcinoma– polyembryoma– nongestational choriocarcinoma– mixed GCT

Teratoma

• Ovarian teratomas are GCTs composed of mature or immature tissues derived from more than one of the three primitive embryonic layers (ectoderm, mesoderm, and endoderm).

Mature Cystic Teratoma

• Often called dermoid cyst when the ectodermal elements predominate, is the most common ovarian tumor in children and adolescents, accounting for approximately 50% of all pediatric ovarian neoplasms.

• MCTs are bilateral in up to 10% of pediatric cases and in 10%–25% of adult cases.

• MCT is associated with various complications including torsion (3%–16%), rupture (1%–4%), infection (1%), and malignant transformation (1%–2%) .

• Most MCTs are unilocular (88%), but some are multilocular.

• Histologically, the neoplasm often has a focal internal protuberance, known as a Rokitansky nodule, that may contain hair, bone, teeth, muscle, or cartilage, and the cyst wall is lined by squamous, respiratory, or gastrointestinal epithelium.

• The characteristic imaging appearance of an ovarian MCT is a cystic adnexal mass that contains fat, but the imaging features vary depending on the histologic composition.

• The most common US finding is a cystic mass with a densely echogenic tubercle (a Rokitansky nodule or dermoid plug) that protrudes into the cystic lumen and shows posterior acoustic shadowing.

• Acoustic shadowing occurs in up to 70% of MCTs, secondary to calcifications or a mixture of hair and adipose tissue in the tubercle.

• Other US findings include a diffusely or partially echogenic mass that represents sebaceous material, multiple thin echogenic bands attributable to hair, fat-fluid levels, floating debris, or a combination of these features

• Although US is diagnostic in most cases, CT or MR imaging should be considered in equivocal cases because these imaging modalities are more sensitive for fat identification.

• At CT, fat attenuation in a cyst, with or without calcification in the cyst wall or Rokitansky nodule, is the characteristic finding.

• A fat-fluid level or a floating mass of hair is occasionally seen.

• At MR imaging, fat is seen in the mass, which is hyperintense on T1-weighted images and shows signal loss on frequency-selective fat-saturated T1-weighted images.

• A small percentage of cases (15%) demonstrate a minimal amount of fat in the cyst wall or Rokitansky nodule and show signal drop with gradient-echo opposed-phase T1- weighted MR sequences.

• Optimal treatment of MCT in the pediatric population is surgical excision with fertility preservation; cystectomy and laparoscopic surgery are preferred for an uncomplicated MCT.

Immature Teratoma

• Immature teratoma typically affects a younger age group; the younger the patient, the more likely that the teratoma will be the immature germ cell type.

• Frequently occurs between the ages of 10 and 20 years, with a median age of 17 years

• Represents 10%–20% of all ovarian malignancies in patients younger than 20 years.

• The neoplasm has a more aggressive behavior and a worse prognosis than does mature teratoma and thus has been treated as malignancy, although it is not truly malignant.

• The current treatment of choice for immature teratoma is surgery with unilateral salpingo-oophorectomy and staging procedure.

• Usually unilateral, large, and predominantly solid.

• Coexisting ipsilateral and contralateral MCTs occur in 26% and 10% of cases of immature teratoma, respectively.

• Histologically, immature teratoma contains a variable amount of primitive immature embryonal tissues derived from three germ cell layers admixed with mature tissues.

• At CT and MR imaging, the tumor typically appears as a large heterogeneous mass with predominantly solid or mixed solid and cystic lesions.

• Scattered calcifications throughout the tumor and punctate foci of fat in the solid components are commonly seen.

• Hemorrhage is occasionally seen.

• Identification of a solid portion with numerous cystic areas is helpful to distinguish immature teratoma from MCT.

Dysgerminoma • Dysgerminoma originates from undifferentiated

germ cells that are similar to primordial germ cells.

• It is the most common malignant GCT in childhood and adolescence.

• Most cases occur in the 2nd and 3rd decades of life, but 10% of cases occur in the 1st decade of life.

• Dysgerminoma is associated with gonadal dysgenesis or abnormal gonads that contain gonadoblastoma.

• An association with chromosomal abnormalities (eg, Turner syndrome) has also been reported.

• LDH is a useful tumor marker for diagnosis and postoperative follow-up. Rarely, serum b-hCG levels are elevated in some tumors that contain differentiated syncytiotrophoblastic cells, which are responsible for endocrine abnormalities.

• In contrast to other malignant GCTs, dysgerminoma is highly radiosensitive.

• Most patients with dysgerminoma (75%) are diagnosed with early-stage disease, and thus surgery alone is curative.

• The prognosis is usually excellent.

• The characteristic imaging appearance of dysgerminoma is a multilobulated solid mass with prominent fibrovascular septa.

• Doppler examination may demonstrate prominent flow signal intensity in the septa.

• Because of their fibrous content, the septa appear as hypointense lines on T2-weighted MR images and may show intense enhancement on contrast-enhanced CT and MR images

• The tumor may also contain necrosis, hemorrhagic foci, or speckled calcifications.

• Unlike other malignant GCTs, dysgerminoma occurs bilaterally in 10%–15% of cases and occasionally spreads to the retroperitoneal lymph nodes.

• Therefore, the contralateral ovary and lymphatic spread should be assessed at diagnosis and follow-up

Yolk Sac Tumor

• Yolk sac tumor, also known as endodermal sinus tumor, is a rare malignant GCT.

• The tumor mostly occurs in the 2nd and 3rd decades of life, at an average age of 19 years.

• Yolk sac tumor is usually aggressive, characterized by rapid growth and extensive spread to the abdominopelvic cavity.

• Both hematogenous and peritoneal metastases are common, and lymphatic spread is not uncommon.

• The tumor produces AFP, which can be used as a tumor marker at initial diagnosis and postoperative follow-up.

• Although the prognosis depends on the disease stage, a yolk sac tumor is usually unilateral early-stage disease.

• Most cases can be treated with conservative surgery and multiagent chemotherapy.

• At CT and MR imaging, a yolk sac tumor appears as a large heterogeneous mass with internal hemorrhage and necrosis.

• MR imaging findings may include striking contrast enhancement of the solid components, intratumoral signal voids, and hemorrhagic areas in the tumor.

• Ascites can also be seen.

• Although these imaging features are not specific, the likelihood of yolk sac tumor should be considered in young patients with an elevated serum AFP level and a large, predominantly solid ovarian mass.

Figure. Yolk sac tumor in an 11-year-old girl. (a) Axial contrast-enhanced CT image shows a large heterogeneous mass (arrows) with nonenhancing necrotic or cystic areas (*). (b) Photograph of the gross specimen shows a large encapsulated solid mass with extensive areas of hemorrhage and necrosis (*). (Scale is in centimeters.)

Figure 8. Yolk sac tumor in an 18-year-old woman. (a) Axial T2-weighted MR image shows a large, well-circumscribed, heterogeneous, hyperintense mass (arrows), with hypointense areas corresponding to intratumoral hemorrhage. Ascites is also seen (*). (b) Axial gadolinium-enhanced T1-weighted MR image of the mass (arrows) shows striking enhancement of the solid components at the periphery (arrowheads).

Embryonal Carcinoma • Embryonal carcinoma is a rare and highly malignant

tumor that accounts for approximately 3% of malignant GCTs.

• The tumor occurs primarily in children and adolescents, with a median age of 14 years.

• Unlike in other malignant GCTs, isosexual precocity or menstrual irregularity related to b-hCG secretion occurs in up to 60% of cases.

• The tumor can produce AFP, b-hCG, or both, which may aid in diagnosis and treatment monitoring.

• Standard staging laparotomy with unilateral salpingo-oophorectomy should be performed, followed by postoperative chemotherapy.

• Histologically, embryonal carcinoma frequently appears mixed with other malignant germ cell types.

• Pure embryonal carcinoma is extremely rare.

• At gross pathologic examination, the tumor manifests as a large, predominantly solid, variegated mass.

• Extensive areas of hemorrhage and necrosis are commonly seen, with cystic spaces containing mucoid materials.

• The cross-sectional imaging appearances are nonspecific and are similar to those of other malignant GCTs.

Epithelial Stromal Tumors

• Constitute 15%–20% of all pediatric ovarian tumors and 60% of ovarian tumors in adult women.

• Epithelial tumors are rare before menarche because hormonal stimulation may trigger their development.

• Although there are numerous histologic subtypes in adults, most pediatric cases are mucinous or serous.

• Further classified as benign, borderline, or malignant on the basis of their histologic and clinical behavior.

Benign Cystadenoma

• The most common type of epithelial tumor in children and adolescents.

• At imaging, benign cystadenomas are typically cystic and either unilocular or multilocular, with a thin wall or septa and no intracystic solid portion.

• In contrast to a serous tumor, mucinous cystadenoma usually appears as a large, multilocular cystic mass that may have fluid-filled locules, with variable attenuation at CT and variable signal intensity at MR imaging.

• Conservative surgery with cystectomy or unilateral oophorectomy is the appropriate treatment.

Borderline and Malignant Epithelial Tumors

• More frequent in children than in adults.

• Rare in girls younger than 14 years, and most cases occur in patients older than 15 years.

• Borderline and malignant epithelial tumors in children and adolescents are usually a low grade and stage; thus, the prognosis is better than in adults with a similar tumor histology.

• At imaging, papillary projections are more commonly found in borderline epithelial tumors (67%) than in benign cystadenomas (13%) and malignant epithelial tumors (38%).

• Malignant epithelial tumors are usually large complex masses with a thick and irregular wall or septa and solid components with necrosis.

• Conservative surgery is recommended for localized tumors.

• Advanced or invasive tumors should be managed with procedures similar to those used in adult women and may result in infertility.

Sex Cord–Stromal Tumors

• Ovarian SCSTs are derived from the coelomic epithelium (sex cords) and ovarian stroma or mesenchyma of the embryonic gonads.

• Ovarian SCSTs are composed of various combinations of granulosa cells, theca cells, Leydig cells, Sertoli cells, and fibroblasts of stromal origin.

• SCSTs account for 10%–20% of all pediatric ovarian tumors and 5%–10% of ovarian neoplasms in all age groups.

• Although ovarian SCSTs occur over a wide age range, they frequently occur in the pediatric age group, particularly in girls younger than 15 years.

• Ovarian SCSTs are classified into four types: – granulosa-stromal cell tumors– Sertoli-stromal cell tumors– SCSTs of mixed or unclassified cell types, and– steroid cell tumors.

• In children and adolescents, granulosa cell tumor and Sertoli-Leydig cell tumor commonly occur, and thecoma-fibromas are rare. Fibroma is the most common SCST in adult women.

• The clinical and diagnostic importance of SCSTs lies in their hormonal activity; granulosa cell tumors and thecomas typically produce estrogen, and Sertoli-Leydig cell tumors are associated with androgenic activity.

Granulosa Cell Tumor Group• Granulosa cell tumors are the most common

malignant SCSTs and are subdivided into adult and juvenile types according to their clinical and histopathologic features.

• Most cases (95%) are adult types; juvenile types constitute only 5% of granulosa cell tumors.

Juvenile Granulosa Cell Tumor• JGCT usually occurs in prepubertal girls and in

women younger than 30 years, with a mean age of 13 years.

• JGCT accounts for 70% of all ovarian SCSTs in patients younger than 20 years. Approximately 80% of prepubertal girls with JGCT present with isosexual precocious puberty related to estrogen secretion.

• Rarely, the tumor produces androgen and can cause virilizing features. In children, JGCT is more frequently associated with acute complications, such as torsion and rupture, than in adults.

• Although a JGCT could appear as an entirely solid or completely cystic mass, most tumors have both solid and cystic components.

• JGCTs have different clinical and histologic features than adult-type tumors, but the two types have similar imaging features because they have the same gross appearance.

• A JGCT typically appears at imaging as a large, unilateral, multicystic mass with a solid portion and sometimes with irregular septa.

• It also can manifest as a solid mass with variable cystic areas or as a predominantly cystic mass with solid portions.

• JGCTs have some distinctive imaging features: a spongelike appearance with solid areas of intermediate signal intensity and numerous cystic spaces on T2-weighted MR images, and hemorrhagic foci of high signal intensity on T1- weighted MR images .

• Uterine enlargement or endometrial thickening may be seen as a result of estrogenic effect.

Figure 9. Granulosa cell tumor in the right ovary of a 14-year-old adolescent girl with galactorrhea and hypermenorrhea. Sagittal T2-weighted MR image shows a well-circumscribed cystic mass (arrows) with a focal mural solid portion (arrowhead).

Figure 10. Granulosa cell tumor in an 18-year-old woman with abdominal distention and menstrual irregularity. Axial T2-weighted MR image shows a well-circumscribed multicystic mass (arrows) with fluid-hemorrhage levels and a spongelike appearance. A small amount of ascites is noted (*).

• Inhibin is a useful serum tumor marker for diagnosis and follow-up. Up to 90% of these tumors are diagnosed as low-stage disease confined to the ovary and usually are curable with conservative surgery alone.

• However, patients with advanced disease or tumors with high mitotic activity have a poorer prognosis and may be treated with chemotherapy.

Thecoma-Fibroma Group • Tumors in the thecoma-fibroma group mostly

occur in adult women older than 30 years and are rare in children and adolescents.

• This tumor group is characterized by fibrous components and includes thecoma, fibroma, cellular fibroma, fibrosarcoma, stromal tumor with minor sex cord elements, sclerosing stromal tumor, signet-ring stromal tumor, and fibrothecoma.

• Thecoma-Fibroma.—

• Thecoma-fibroma represents less than 2% of all pediatric ovarian tumors.

• A thecoma is a benign stromal tumor composed of lipid-containing theca cells and a variable amount of fibroblasts.

• Approximately 50% of these tumors are estrogenic. Unlike thecoma, ovarian fibroma, which arises from spindle collagen-producing cells, is rarely associated with hormone production.

• Most cases are benign, and surgical resection is curative.

• Ovarian thecoma and fibroma usually appear as solid masses. At CT and MR imaging, these tumors are seen as homogeneous solid tumors with delayed or variable contrast enhancement, depending on the amount of fibrous content.

• Calcifications are often seen in a fibroma. A fibroma typically has low signal intensity on T1-weighted MR images and very low signal intensity on T2-weighted MR images because of the abundant collagen content. On T2-weighted MR images, scattered hyperintense areas in the mass represent edema or cystic degeneration.

• Consideration should be given to torsion if the tumor has no or poor contrast enhancement.

• Fibromas can be seen with ascites and right-sided pleural effusion, findings suggestive of Meigs sydrome.

Sclerosing Stromal Tumor• Sclerosing stromal tumor is a rare benign stromal

tumor that is included in the thecoma-fibroma group in the most recent World Health Organization classification.

• Most patients are younger than 30 years (70%), and the median age at diagnosis for children and adolescents is 13 years. Although this tumor is usually hormonally inactive, it may have an estrogenic and rarely an androgenic effect, which may be seen in up to 50% of cases in the pediatric population.

• Bilateral tumors have been reported in a patient with Gorlin syndrome.

• At CT and MR imaging, the tumor appears well-circumscribed and mixed cystic and solid, with central edema or cleftlike cysts (Fig 11).

• On T2-weighted MR images, the solid portion, composed of packed cells, has low signal intensity, whereas the interposed stroma with edema or mucoid degeneration has high signal intensity.

• A thin hypointense rim of compressed ovarian cortex can also be seen. At dynamic contrast-enhanced MR imaging, the tumor demonstrates early peripheral enhancement with centripetal progression, which reflects prominent vascularity in the periphery and a hypocellular edematous stroma in the inner portion of the tumor.

Figure. Sclerosing stromal tumor in an 11-year-old girl with deepening of the voice and hirsutism.

(a) Axial T2-weighted MR image shows a well-circumscribed mass with intermediate signal intensity. Multifocal hyperintense foci are seen (arrowheads).

(b) Axial gadolinium-enhanced T1-weighted MR image shows intense enhancement of the mass, with nonenhancing areas (arrowheads) that represent small cysts or clefts.

(c) Photograph of the gross specimen shows a yellow to pink solid mass with whitish streaks of fibrous stroma and small cysts (arrowheads). (Scale is in centimeters.)

Sertoli-Leydig Cell Tumor • Sertoli-Leydig cell tumor, which is included in the category of

Sertoli-stromal cell tumors, is a rare stromal tumor that accounts for less than 0.5% of all malignant ovarian neoplasms in children.

• These tumors usually occur in women younger than 30 years, with a median age of 14 years.

• This tumor is the most common androgen-producing ovarian tumor; approximately 30% of cases are associated with androgenic activity.

• Precocious puberty rarely is reported in premenarcheal girls.

• Histologically, the tumor is classified into well-differentiated, intermediately differentiated, poorly differentiated, and retiform subtypes. All except the well-differentiated subtype may contain heterologous elements, of which hepatic differentiation is responsible for elevated serum AFP levels.

• Most of these tumors are diagnosed as early-stage and low-grade malignant tumors, and the prognosis is usually good.

• Sertoli-Leydig cell tumor has a varied gross appearance, including solid, partially cystic, or completely cystic.

• It typically appears as a predominantly solid mass with peripheral or intratumoral cysts or as a cystic mass with solid mural portions.

• At T2-weighted MR imaging, the solid components show variable signal intensity, depending on the extent of fibrous stroma.

Figure 12. Sertoli-Leydig cell tumor in a 3-year-old girl with abnormal vaginal bleeding and breast enlargement. (a) Sagittal reformatted contrast-enhanced CT image shows a large complex mass (arrows) with solid and cystic components. Note the uterine enlargement (arrowheads) due to the tumor’s estrogenic effect. (b) Photograph of the gross specimen shows a yellow-tan solid mass with cystic cavities (C).

Figure 13. Sertoli-Leydig cell tumor in a 12-year-old girl with abdominal distention and hirsutism. (a) Axial transabdominal US image shows a multilocular cystic mass (arrows) with mural echogenic solid portions (S). (b) Axial gadolinium-enhanced T1-weighted MR image shows contrast enhancement of the solid components (S) of the mass (arrows). Note the normal appearance of the right ovary (arrowhead) and the large amount of ascites.

Conclusions

• Primary ovarian tumors in children and adolescents are uncommon and include a diverse group of benign and malignant tumors. The incidence, histologic distribution, and clinical presentation of these tumors are distinct from those in adults. Some types of ovarian tumors are associated with abnormal hormonal activity and/ or abnormal sexual development.

• Evaluation of serum tumor markers and karyotyping can assist in differential diagnosis.

• Imaging features at US, CT, and MR imaging can help in differentiating benign from malignant ovarian tumors and determining treatment options.

• Preserving future fertility and selecting the appropriate surgical procedure are crucial in children and adolescents. The differential diagnosis should be made on the basis of unique clinical manifestations and elevated serum tumor markers in conjunction with distinctive imaging features.

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