Defintion

A germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or
non-cancerous tumors. Germ cells normally occur inside the gonads (ovary and testis). Germ cell tumors
that originate outside the gonads may be birth defects resulting from errors during development of the
embryo.

Etiology

Some investigators suggest that this distribution arises as a consequence of abnormal migration
of germ cells during embryogenesis. Others hypothesize a widespread distribution of germ cells
to multiple sites during normal embryogenesis, with these cells conveying genetic information
or providing regulatory functions at somatic sites.

Extragonadal germ cell tumors were thought initially to be isolated metastases from an
undetected primary tumor in a gonad, but it is now known that many germ cell tumors are
congenital and originate outside the gonads. The most notable of these is sacrococcygeal
teratoma, the single most common tumor diagnosed in babies at birth.

Classification

Germ cell tumors are classified by their histology,[1] regardless of location in the body.

Germ cell tumors are broadly divided in two classes:[2]

 The germinomatous or seminomatous germ cell tumors (GGCT, SGCT) include only
germinoma and its synonyms dysgerminoma and seminoma.
 The nongerminomatous or nonseminomatous germ cell tumors (NGGCT, NSGCT)
include all other germ cell tumors, pure and mixed.

The two classes reflect an important clinical difference. Compared to germinomatous tumors,
nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis
(~25 years versus ~35 years, in the case of testicular cancers), and have a lower 5 year survival
rate. The survival rate for germinomatous tumors is higher in part because these tumors are
exquisitely sensitive to radiation, and they also respond well to chemotherapy. The prognosis
for nongerminomatous has improved dramatically, however, due to the use of platinum-based
chemotherapy regimens.[3]
Germinomatous

Peak
Benign or Tumor
Tumor ICD-O Age Histology
malignant marker
(yr)
Germinoma (including Sheets of uniform polygonal 10% have
dysgerminoma and 40-50 Malignant cells with cleared cytoplasm; elevated
seminoma) lymphocytes in the stroma hCG
Dysgerminoma M9061/3
Seminoma M9060/3

Nongerminomatous

Peak
Benign or Tumor
Tumor ICD-O Age Histology
malignant marker
(yr)
Pure
Poorly differentiated,
tumors do
pleomorphic cells in
Embryonal carcinoma 9070/3 20-30 Malignant not
cords, sheets, or
secrete
papillary formation
hCG, AFP
Poorly differentiated
Endodermal sinus tumor, 100%
endothelium-like,
also known as yolk sac 9071/3 3 Malignant secrete
cuboidal, or columnar
tumor (EST, YST) AFP
cells
Cytotrophoblast and 100%
Choriocarcinoma 9100/3 20-30 Malignant syncytiotrophoblast secrete
without villus formation hCG
Mature teratoma,
Teratoma including Pure
dermoid cyst
mature teratoma, Very variable, but tumors do
9080/0- 0-3, usually benign
dermoid cyst, immature "normal" tissues are not
9080/3 15-30 (but follow-up
teratoma, teratoma with common secrete
required); others
malignant transformation hCG, AFP
usually malignant

Location

Despite their name, germ cell tumors occur both within and outside the ovary and testis.

 head
 o inside the cranium — pineal and suprasellar locations are most commonly
reported
o inside the mouth — a fairly common location for teratoma
 neck
 1% to 5% in the mediastinum (mediastinal germ cell tumor)
 pelvis, particularly sacrococcygeal teratoma

 ovary

Main article: Ovarian cancer

 testis

In females, germ cell tumors account for 30% of ovarian tumors, but only 1 to 3% of ovarian
cancers in North America. In younger women germ cell tumors are more common, thus in
patients under the age of 21, 60% of ovarian tumors are of the germ cell type, and up to one-
third are malignant. In males, germ cell tumors of the testis occur typically after puberty and
are malignant (testicular cancer). In neonates, infants, and children younger than 4 years, the
majority of germ cell tumors are sacrococcygeal teratomas.

Males with Klinefelter's syndrome have a 50 times greater risk of germ cell tumors (GSTs) [5]. In
these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and
seldom are gonadal in location.

Prognosis

The 1997 International Germ Cell Consensus Classification[6] is a tool for estimating the risk of
relapse after treatment of malignant germ cell tumor.

A small study of ovarian tumors in girls[7] reports a correlation between cystic and benign
tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can
be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most
appropriate surgical plan to minimize risk of spillage of a malignant tumor.

Access to appropriate treatment has a large effect on outcome. A 1993 study of outcomes in
Scotland found that for 454 men with non-seminomatous (non-germinomatous) germ cell
tumors diagnosed between 1975 and 1989, 5-year survival increased over time and with earlier
diagnosis. Adjusting for these and other factors, survival was 60% higher for men treated in a
cancer unit that treated the majority of these men, even though the unit treated more men
with the worst prognosis

What are the symptoms of germ cell tumors?

The following are the most common symptoms of germ cell tumors. However, each child may
experience symptoms differently. Symptoms vary depending on the size and location of the
tumor. Symptoms may include:

 a tumor, swelling, or mass that can be felt or seen

 elevated levels of alpha-fetoprotein (AFP)

 elevated levels of beta-human chorionic gonadotropin (β-HCG)

 constipation, incontinence, and leg weakness can occur if the tumor is in the sacrum (a
segment of the vertebral column that forms the top part of the pelvis) compressing
structures

 abnormal shape, or irregularity in, testicular size

The symptoms of germ cell tumors may resemble other conditions or medical problems. Always
consult your child's physician for a diagnosis.

How are germ cell tumors diagnosed?

In addition to a complete medical history and physical examination, diagnostic procedures for
germ cell tumors may include:

 biopsy - a sample of tissue is removed from the tumor and examined under a
microscope.

 complete blood count (CBC) - a measurement of size, number, and maturity of different
blood cells in a specific volume of blood.

 additional blood tests - may include blood chemistries, evaluation of liver and kidney
functions, and genetic studies.

 multiple imaging studies, including:

o computed tomography scan (Also called a CT or CAT scan.) - a diagnostic

imaging procedure that uses a combination of x-rays and computer technology
to produce cross-sectional images (often called slices), both horizontally and
vertically, of the body. A CT scan shows detailed images of any part of the body,
including the bones, muscles, fat, and organs. CT scans are more detailed than
general x-rays.
 o magnetic resonance imaging (MRI) - a diagnostic procedure that uses a
combination of large magnets, radiofrequencies, and a computer to produce
detailed images of organs and structures within the body.

o x-ray - a diagnostic test which uses invisible electromagnetic energy beams to

produce images of internal tissues, bones, and organs onto film.

o ultrasound (Also called sonography.) -a diagnostic imaging technique which uses

high-frequency sound waves and a computer to create images of blood vessels,
tissues, and organs. Ultrasounds are used to view internal organs as they
function, and to assess blood flow through various vessels.

o bone scans - pictures or x-rays taken of the bone after a dye has been injected
that is absorbed by bone tissue. These are used to detect tumors and bone
abnormalities.

What are the different types of germ cells?

Diagnosis of germ cell tumors depends on the types of cells involved. The most common types
of germ cell tumors include:

 teratomas
Teratomas contain cells from the three germ layers: ectoderm, mesoderm, and
endoderm. Teratomas can be malignant or benign, depending on the maturity and other
types of cells that may be involved. Teratomas are the most common germ cell tumor
found in the ovaries. Sacrococcygeal (tail bone, or distal end of spinal column)
teratomas are the most common germ cell tumors found in childhood. Because these
sacrococcygeal tumors are often visible from the outside of the body, diagnosis is made
early and treatment and/or surgery are initiated early, making the prognosis for this
type of germ cell tumor very favorable.

 germinomas
Germinomas are malignant germ cell tumors. Germinomas are also termed
dysgerminoma when located in the ovaries; and seminoma when located in the testes.
Among children, germinoma, or dysgerminoma, occurs most frequently in the ovary of a
pre-pubescent or adolescent female. Dysgerminoma is the most common malignant
ovarian germ cell tumor seen in children and adolescents.
  endodermal sinus tumor or yolk sac tumors
Endodermal sinus tumor or yolk sac tumors are germ cell tumors that are most often
malignant, but may also be benign. These tumors are most commonly found in the
ovary, testes, and sacrococcygeal areas (tail bone, or distal end of spinal column). When
found in the ovaries and testes, they are often very aggressive, malignant, and can
spread rapidly through the lymphatic system and other organs in the body. Yolk sac
tumors are the most common malignant testicular and ovarian tumors in children. Most
yolk sac tumors will require surgery and chemotherapy, regardless of stage or presence
of metastasis, because of the aggressive nature and recurrence of the disease.

 choriocarcinoma
Choriocarcinoma is a very rare, but often malignant germ cell tumor that arises from the
cells in the chorion layer of the placenta (during pregnancy, a blood-rich structure
through which the fetus takes in oxygen, food, and other substances while getting rid of
waste products). These cells may form a tumor in the placental cells during pregnancy
and spread (metastasize) to the infant and mother. When the tumor develops during
pregnancy, it is called gestational choriocarcinoma. Gestational choriocarcinoma most
often occurs in pregnant females that are 15 to19 years of age. If a non-pregnant young
child develops choriocarcinoma from the chorion cells that originated from the placenta
that are still in the body, the term used is non-gestational choriocarcinoma.

 embryonal carcinoma
Embryonal carcinoma cells are malignant cells that are usually mixed with other types of
germ cell tumors. They occur most often in the testes. These types of cells have the
ability to spread to other parts of the body. When these cells are mixed with an
otherwise benign type of tumor (mature teratoma), the presence of embryonal
carcinoma cells will cause it to become malignant (cancerous).

Many germ cell tumors have multiple types of cells involved. The diagnosis, treatment, and
prognosis are based on the most malignant of the cells present and the majority type of cells
that are present.

Treatment for germ cell tumors:

Specific treatment for germ cell tumors will be determined by your child's physician based on:

 your child's age, overall health, and medical history

 extent of the disease
 your child's tolerance for specific medications, procedures, or therapies
 expectations for the course of the disease
 your opinion or preference

Treatment may include (alone or in combination):

 surgery (to remove tumor and involved organs)

 chemotherapy

 radiation

 bone marrow transplantation

 supportive care (for the effects of treatment)

 hormonal replacement (if necessary)

 antibiotics (to prevent/treat infections)

 continuous follow-up care (to determine response to treatment, detect recurrent

disease, and manage the late effects of treatment)