The classification of malignant ovarian germ cell tumors is modified from the 2003 World Health Organization

histologic classification of tumors of the ovary (see Table 3). [4, 5]

Table 3. Classification of Malignant Ovarian Germ Cell Tumors (Open Table in a new window)
Dysgerminoma

Yolk sac tumor

Embryonal carcinoma

Primitive germ cell tumors

Polyembryoma

Nongestational choriocarcinoma

Mixed germ cell tumor, specify components

Immature teratoma

Biphasic or triphasic teratomas

Mature teratoma (benign)

Monodermal teratoma and somatic-type tumors associated with mature teratoma

Thyroid tumor group

Carcinoid group

Neuroectodermal tumor group

Carcinoma group

Melanocytic group

Sarcoma group

Sebaceous tumor group

Pituitary-type tumor group

Retinal anlage tumor group

Other

Definition
Yolk sac tumors are those that resembles the yolk sac, allantois, and extraembryonic mesenchyme. They are
also known as endodermal sinus tumors.

Epidemiology
Yolk sac tumors (YSTs) can be seen in males and females, involving the testis, ovary, and other sites, such as
the mediastinum. Yolk sac tumors (YSTs) of the testis are observed in 2 forms or age groups: pure YST in
young children and mixed type in adults.
Pure yolk sac tumor (YST) is the most common testicular neoplasm in prepubertal children, accounting for 80%
of testicular germ cell tumors in this age group, with a median age of 1.5 years. In adults, yolk sac tumor (YST)
presents as a component of mixed nonseminomatous germ cell tumor, with an age averaging 25-30 years. Yolk
sac tumor (YST) components are present in 40-50% of nonseminomatous germ cell tumors in the adult testis. [1,
2]

In children, yolk sac tumors (YSTs) are more common in Asians than in white or black persons. In adults, these
tumors are more common in white individuals than in other races.

Etiology
The etiology of yolk sac tumors (YSTs) is essentially unknown. It is speculated that hypermethylation of
the RUNX3 gene promoter and overexpression of GATA-4, a transcription factor that regulates differentiation
and function of yolk sac endoderm, may play important roles in the pathogenesis of yolk sac tumors (YSTs). [3,
4]
However, these hypotheses have not been validated.

Location
Yolk sac tumors (YSTs) of the testis are located in the testis parenchyma.

Clinical Features and Imaging

Children with yolk sac tumors (YSTs) usually present with painless testicular masses, which are typically bulky
lesions. Metastasis is uncommon at presentation, occurring in less than 10% of cases. In adults, yolk sac
tumors (YSTs) are associated with other germ cell components such as embryonal carcinoma,
choriocarcinoma, teratoma, and seminoma as a part of a mixed germ cell tumor. No specific symptoms except
testicular mass are present. Almost all the patients with a yolk sac tumor (YST), either in pure form or mixed
form have a significantly elevated serum alpha fetoprotein (AFP).
The presence of hair, bone, or cartilage (the elements of a teratoma) can be seen in a testicular mass in adults
by radiographic examination, which may or may not be associated with yolk sac tumor (YST) components. The
radiographic findings are specific for malignant mixed germ cell tumors but are not specific for yolk sac tumors
(YSTs).
Li et al investigate computed tomography (CT) findings of yolk sac tumors with pathological correlation. The
study concludes that 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. [5]

Gross Findings
Grossly, yolk sac tumors (YSTs) are solid gray-white with a gelatinous, myxoid, or mucoid appearance.
Necrosis, cystic changes, and hemorrhage are often seen. In adults, the gelatinous appearance of these
tumors is mingled with the gross findings of the other germ cell tumor components; therefore, the overall
appearance of a yolk sac tumor (YST) is heterogeneous.

Microscopic Findings
Yolk sac tumor (YST) of the testis is composed of primitive tumor cells, which are relatively small and less
pleomorphic relative to those in embryonal carcinoma, another common subtype of malignant germ cell tumor
of the testis.
YST cells may form many histologic patterns resembling embryonal structures. The most common pattern seen
in the majority cases of these tumors is microcystic structure, which is characterized by the presence of a
spider-weblike network formed by vacuolated cytoplasm of tumor cells, similar to a honeycomb (see the image
below).

Microcystic pattern of yolk sac tumors. The

tumor cells form a network connected by cytoplasm.

Other patterns include endodermal sinus (perivascular), papillary, solid, glandular, festoon, myxomatous,
sarcomatoid, macrocytic, polyvesicular, hepatoid, and parietal. These patterns do not relate to prognosis but
can cause difficulty in distinguishing yolk sac tumors (YSTs) from other tumors or other subtypes of germ cell
tumors.[1]
The endodermal sinus pattern consists of a central vessel rimmed by fibrous tissue, surrounded by malignant
epithelial cells in a cystic space which is lined by flattened tumor cells. This endodermal sinuslike structure is
called a Schiller-Duvall body and is pathognomonic of yolk sac tumors (YSTs) (see the following image);
however, Schiller-Duvall bodies are present only in 50-75% of these tumors.

Schiller-Duvall body. A Schiller-Duvall body is a

structure resembling the endodermal sinus, characterized by the presence of a central vessel, surrounded by fibrous tissue
and epithelial tumor cells, in a space lined by flat tumor cells.

Hyaline globules ranging from 1 to 50 microns can be seen in yolk sac tumors (YSTs), which are periodic acidSchiff stain (PAS) positive and diastase-resistant. Occasionally, the hyaline globules can be positive for AFP.
Eosinophilic bands (extracellular basement membrane material) are frequent findings in yolk sac tumors
(YSTs). Either hyaline globules or eosinophilic bands are specific for these tumors.

Immunohistochemistry
Yolk sac tumor (YST) cells are positive for AFP, which can be detected on tissue sections as well as in the
serum of the patients with these tumors.[6] However, AFP is not specific for yolk sac tumors (YSTs), as other
tumors such as hepatocellular carcinoma and hepatoblastoma can also be positive for APF.[7] Cytokeratin is
present in almost all the cases, and vimentin can be positive in spindle cell patterns. Approximately 40-80% of
cases of yolk sac tumors (YSTs) are positive for placental alkaline phosphatase (PLAP), a marker of several
different subtypes of germ cell tumors.
In the past few years, other markers of yolk sac tumors (YSTs) have been reported. A promising marker that
has been identified is glypican 3, which is a membrane-bound heparan sulfate proteoglycan. As a marker for
yolk sac tumors (YSTs), glypican 3 is more sensitive but less specific than AFP, as glypican 3 can be detected
in choriocarcinoma (which will be discussed in a separate pathology article) and a small percentage of
immature teratomas, in addition to liver cancers.[8]

Molecular/Genetics
Chromosomal changes
The loss of the short arm of chromosome 1 (1p36) and the long arm of chromosome 6 (6q) as well as gain of
the long arm of chromosomes 1 and 20 have been reported in yolk sac tumors (YSTs). In addition,
isochromosome 12p, which is characteristic of other malignant testicular germ cell tumors, can be detected.

Expression signature
There is limited information in the literature regarding the gene expression signatures of yolk sac tumors
(YSTs). However, a few papers have demonstrated the molecular signature of these tumors based on
expression from microarrays studies.[9]

Tumor Spread and Staging

Of children with yolk sac tumors (YSTs), 80-90% of the tumors are stage I disease. The presence of a yolk sac
tumor (YST) component in stage I tumors has been associated with decreased likelihood of occult metastasis.

Prognosis and Predictive Factors

Without treatment, this tumor is highly aggressive in children and will lead to death. With a combination of
modern surgical treatment and adjuvant chemotherapy (cisplatin-based), the survival rate in those with yolk sac
tumors (YSTs) is greater than 90%. The prognosis of a malignant germ cell tumor in adults with a YST
component is dependent on the response of the YST as well as other components to therapy.
Age at diagnosis is not a predictive factor in yolk sac tumors (YSTs), but the degree of AFP elevation, in
addition to other serum tumor markers in mixed germ cell tumors, has been shown to correlate with prognosis.
For serum AFP, levels < 1000 ng/mL are in the good prognostic category, levels >10,000 ng/mL are in the poor
prognostic category, and those in between these levels are associated with an intermediate prognosis. Stage is
also an important prognostic factor; early detection of lower stage disease will result in better prognosis .

Differentials
Embryonal carcinoma (EC) should be distinguished from yolk sac tumors (YSTs), because EC is more
pleomorphic, and lacks the special patterns of YST.
Seminoma should be distinguished from the solid pattern of yolk sac tumors (YSTs). Seminoma cells are bigger
that YST cells, with lymphocytic infiltrates.
Juvenile granulosa cell tumor (JGCT) should be distinguished from yolk sac tumors (YSTs) because of their
morphologic similarities. JGCT is seen female children younger than 5 months old. Although microcystic
patterns can be seen in JGCT, the other patterns of YST cannot be found in JGCT.