Teratoma

From Wikipedia, the free encyclopedia

Jump to navigationJump to search

Teratoma

A small (4 cm) dermoid cyst of an ovary, discovered during Cesarean

section

Specialty Gynecology, oncology

Symptoms Minimal, painless lump[1][2]

Complications Ovarian torsion, testicular torsion, hydrops

fetalis[1][2][3]

Types Mature, immature[4]

Causes Unknown[2]

Diagnostic method Tissue biopsy[2]

Differential Lipoma, dermoid, myelomeningocele[5]

diagnosis
 Treatment Surgery, chemotherapy[5][6]

Frequency 1 in 30,000 newborns (coccyx)[7]

A teratoma is a tumor made up of several different types of tissue, such

as hair, muscle, teeth, or bone.[4] Teratomata typically form in the ovary, testicle,
or coccyx.[4]

Contents

 1Symptoms
 2Types
o 2.1Mature teratoma
o 2.2Immature teratoma
o 2.3Gliomatosis peritoneii
o 2.4Dermoid cyst
o 2.5Fetus in fetu and fetiform teratoma
o 2.6Struma ovarii
o 2.7Epignathus
 3Signs and symptoms
o 3.1Complications
 4Pathophysiology
o 4.1Hypotheses of origin
 5Diagnosis
o 5.1Classification
 6Treatment
o 6.1Surgery
o 6.2Chemotherapy
o 6.3Follow-up
 7Epidemiology
 8Other animals
 9Use in stem cell research
 10References
 11External links

Symptoms[edit]
Symptoms may be minimal if the tumor is small.[2] A testicular teratoma may present as
a painless lump.[1] Complications may include ovarian torsion, testicular torsion,
or hydrops fetalis.[1][2][3]
They are a type of germ cell tumor (a tumor that begins in the cells that give rise
to sperm or eggs).[4][8] They are divided into two types: mature and immature. [4] Mature
teratomas include dermoid cysts and are generally benign.[8] Immature teratomas may
be cancerous.[4][9] Most ovarian teratomas are mature.[10] In adults, testicular teratomas
are generally cancerous.[11] Definitive diagnosis is based on a tissue biopsy.[2]
Treatment of coccyx, testicular, and ovarian teratomas is generally by surgery. [5][6]
[12]
 Testicular and immature ovarian teratomas are also frequently treated
with chemotherapy.[6][10]
Teratomas occur in the coccyx in about one in 30,000 newborns, making them one of
the most common tumors in this age group.[5][7] Females are affected more often than
males.[5] Ovarian teratomas represent about a quarter of ovarian tumors and are typically
noticed during middle age.[10] Testicular teratomas represent almost half of testicular
cancers.[13] They can occur in both children and adults. [14] The term comes from the Greek
word for "monster"[15] plus the "-oma" suffix used for tumors.

Types[edit]
Mature teratoma[edit]

Ovarian teratoma with hair inside

Mature teratoma of the mediastinum: A horizontal slice of the resected tumor reveals fibrofatty tissue, calcified
areas, and a few cystic spaces lined with smooth membrane and containing a hair. In the left lower corner, the
involved B5 bronchus is evident.

A mature teratoma is a grade 0 teratoma. They are highly variable in form and histology,
and may be solid, cystic, or a combination of the two. A mature teratoma often contains
several different types of tissue such as skin, muscle, and bone. Skin may surround a
cyst and grow abundant hair (see dermoid cyst). Mature teratomas generally are
benign, with 0.17-2% of mature cystic teratomas becoming malignant. [16]
Immature teratoma[edit]
Immature teratoma is the malignant counterpart of the mature teratoma and contains
immature tissues which typically show primitive or embryonal neuroectodermal
histopathology. Immature teratoma has one of the lowest rates of somatic mutation of
any tumor type and results from one of five mechanisms of meiotic failure. [17]
Gliomatosis peritoneii[edit]
Gliomatosis peritoneii, which presents as a deposition of mature glial cells in the
peritoneum, is almost exclusively seen in conjunction with cases of ovarian teratoma.
Through genetic studies of exome sequence, it was found that gliomatosis is genetically
identical to the parent ovarian tumor and developed from cells that disseminate from the
ovarian teratoma.[17]
Dermoid cyst[edit]
A dermoid cyst is a mature cystic teratoma containing hair (sometimes very abundant)
and other structures characteristic of normal skin and other tissues derived from
the ectoderm. The term is most often applied to teratoma on the skull sutures and in the
ovaries of females.[citation needed]
Fetus in fetu and fetiform teratoma[edit]
Fetus  in fetu and fetiform teratoma are rare forms of mature teratomas that include one
or more components resembling a malformed fetus. Both forms may contain or appear
to contain complete organ systems, even major body parts such as a torso or limbs.
Fetus in fetu differs from fetiform teratoma in having an apparent spine and bilateral
symmetry.[18]
Most authorities agree that fetiform teratomas are highly developed mature teratomas;
the natural history of fetus in fetu is controversial.[18] There also may be a cultural
difference, with fetiform teratoma being reported more often in ovarian teratomas (by
gynecologists) and fetus in fetu being reported more often in retroperitoneal teratomas
(by general surgeons). Fetus in fetu has often been interpreted as a fetus growing within
its twin. As such, this interpretation assumes a special complication of twinning, one of
several grouped under the term parasitic twin. In this regard, in many cases the fetus in
fetu is reported to occupy a fluid-filled cyst within a mature teratoma. [19][20][21][22] Cysts within
mature teratoma may have partially developed organ systems; reports include cases of
partial cranial bones, long bones and a rudimentary beating heart.[23][24]
Regardless of whether fetus in fetu and fetiform teratoma are one entity or two, they are
distinct from and not to be confused with ectopic pregnancy.
Struma ovarii[edit]
Main article: Struma ovarii
A struma ovarii (also known as goitre of the ovary or ovarian goiter) is a rare form of
mature teratoma that contains mostly thyroid tissue.[25]
Epignathus[edit]
Main article: Epignathus
Epignathus is a rare teratoma originating in oropharyngeal area that occurs in utero. It
presents with a mass protruding from the mouth at birth. Untreated, breathing is
impossible. An EXIT procedure is the recommended initial treatment.

Signs and symptoms[edit]

Teratomas may be found in babies, children, and adults. Teratomas of embryonal origin
are most often found in babies at birth, in young children, and, since the advent
of ultrasound imaging, in fetuses.
The most diagnosed fetal teratomas are sacrococcygeal teratoma (Altman types I, II,
and III) and cervical (neck) teratoma. Because these teratomas project from the fetal
body into the surrounding amniotic fluid, they can be seen during routine prenatal
ultrasound exams. Teratomas within the fetal body are less easily seen with ultrasound;
for these, MRI of the pregnant uterus is more informative. [26][27]
Complications[edit]
Teratomas are not dangerous for the fetus unless either a mass effect occurs or a large
amount of blood flows through the tumor (known as vascular steal). The mass effect
frequently consists of obstruction of normal passage of fluids from surrounding organs.
The vascular steal can place a strain on the growing heart of the fetus, even resulting in
heart failure, thus must be monitored by fetal echocardiography.
Teratomas can cause an autoimmune illness called N-methyl-D-aspartate (NMDA)
receptor encephalitis. In this condition, the teratomas may contain B cells with NMDA-
receptor specificities.[28]
After surgery, a risk exists of regrowth in place, or in nearby organs. [29]

Pathophysiology[edit]
Main article: Germ cell tumor
Teratomas belong to a class of tumors known as nonseminomatous germ cell tumor. All
tumors of this class are the result of abnormal development of pluripotent cells: germ
cells and embryonal cells. Teratomas of embryonic origin are congenital; teratomas of
germ cell origin may or may not be congenital. The kind of pluripotent cell appears to be
unimportant, apart from constraining the location of the teratoma in the body.
Teratomas derived from germ cells occur in the testicle in men and ovaries in women.
Teratomas derived from embryonic cells usually occur on the subject's midline: in the
brain, elsewhere in the skull, in the nose, in the tongue, under the tongue, and in
the neck (cervical teratoma), mediastinum, retroperitoneum, and attached to the coccyx.
Teratomas may also occur elsewhere: very rarely in solid organs (most notably the
heart and liver) and hollow organs (such as the stomach and bladder), and more
commonly on the skull sutures.
Teratoma rarely include more complicated body parts such as teeth, brain matter,
[30]
 eyes,[31][32] or torso.[33]
Hypotheses of origin[edit]
Concerning the origin of teratomas, numerous hypotheses exist. [18] These hypotheses
are not to be confused with the unrelated hypothesis that fetus in fetu (see below) is not
a teratoma at all, but rather a parasitic twin.

Diagnosis[edit]

CT showing a teratoma of the ovary: fatty formation with a smooth boundary, with a dense part, possibly a
tooth.

Micrograph of a teratoma showing tissue from all three germ layers: mesoderm (immature cartilage - left-

upper), endoderm (gastrointestinal glands - center-bottom) and ectoderm (epidermis - right)

Teratomas are thought to originate in utero, so can be considered congenital tumors.

Many teratomas are not diagnosed until much later in childhood or in adulthood. Large
tumors are more likely to be diagnosed early on. Sacrococcygeal and cervical
teratomas are often detected by prenatal ultrasound. Additional diagnostic methods may
include prenatal magnetic resonance imaging. In rare circumstances, the tumor is so
large that the fetus may be damaged or die. In the case of large sacrococcygeal
teratomas, a significant portion of the fetus' blood flow is redirected toward the teratoma
(a phenomenon called steal syndrome), causing heart failure, or hydrops, of the fetus.
In certain cases, fetal surgery may be indicated.
Beyond the newborn period, symptoms of a teratoma depend on its location and organ
of origin. Ovarian teratomas often present with abdominal or pelvic pain, caused
by torsion of the ovary or irritation of its ligaments. A recently discovered condition
where ovarian teratomas cause encephalitis associated with antibodies against the N-
methyl-D-aspartate receptor antibody (NMDAR) - often referred to as "anti-NMDA
receptor encephalitis", was identified as a serious complication. Patients develop a
multistage illness that progresses from psychosis, memory deficits, seizures, and
language disintegration into a state of unresponsiveness with catatonic features often
associated with abnormal movements, and autonomic and breathing instability.
[34]
 Testicular teratomas present as a palpable mass in the testis; mediastinal teratomas
often cause compression of the lungs or the airways and may present with chest
pain and/or respiratory symptoms.
Some teratomas contain yolk sac elements, which secrete alpha-fetoprotein. Its
detection may help to confirm the diagnosis and is often used as a marker for
recurrence or treatment efficacy, but is rarely the method of initial diagnosis. (Maternal
serum alpha-fetoprotein is a useful screening test for other fetal conditions,
including Down syndrome, spina bifida, and abdominal wall defects such
as gastroschisis.)
Classification[edit]
Regardless of location in the body, a teratoma is classified according to a cancer
staging system. This indicates whether chemotherapy or radiation therapy may be
needed in addition to surgery. Teratomas commonly are classified using the Gonzalez-
Crussi[18] grading system: 0 or mature (benign); 1 or immature, probably benign; 2 or
immature, possibly malignant (cancerous); and 3 or frankly malignant. If frankly
malignant, the tumor is a cancer for which additional cancer staging applies. [citation needed]
Teratomas are also classified by their content; a solid teratoma contains only tissues
(perhaps including more complex structures); a cystic teratoma contains only pockets of
fluid or semifluid such as cerebrospinal fluid, sebum, or fat; a mixed teratoma contains
both solid and cystic parts. Cystic teratomas usually are grade 0 and, conversely, grade
0 teratomas usually are cystic.
Grades 0, 1, and 2 pure teratomas have the potential to become malignant (grade 3),
and malignant pure teratomas have the potential to metastasize. These rare forms of
teratoma with malignant transformation may contain elements of somatic (not germ cell)
malignancy such as leukemia, carcinoma, or sarcoma.[35] A teratoma may contain
elements of other germ cell tumors, in which case it is not a pure teratoma, but rather is
a mixed germ cell tumor and is malignant. In infants and young children, these elements
usually are endodermal sinus tumor, followed by choriocarcinoma. Finally, a teratoma
can be pure and not malignant yet highly aggressive; this is exemplified by growing
teratoma syndrome, in which chemotherapy eliminates the malignant elements of a
mixed tumor, leaving pure teratoma, which paradoxically begins to grow very rapidly. [36]
Malignant transformation[edit]
A "benign" grade 0 (mature) teratoma nonetheless has a risk of malignancy.
Recurrence with malignant endodermal sinus tumor has been reported in cases of
formerly benign mature teratoma,[37][38] even in fetiform teratoma and fetus in fetu.[39]
[40]
 Squamous cell carcinoma has been found in a mature cystic teratoma at the time of
initial surgery.[41] A grade 1 immature teratoma that appears to be benign (e.g., because
AFP is not elevated) has a much higher risk of malignancy, and requires adequate
follow-up.[42][43][44][45] This grade of teratoma also may be difficult to diagnose correctly. It can
be confused with other small round cell neoplasms such as neuroblastoma, small cell
carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor,
desmoplastic small round cell tumor, and non-Hodgkin lymphoma.[46]
A teratoma with malignant transformation is a very rare form of teratoma that may
contain elements of somatic malignant tumors such as leukemia, carcinoma, or
sarcoma.[35] Of 641 children with pure teratoma, nine developed TMT: [47] five carcinoma,
two glioma, and two embryonal carcinoma (here, these last are classified among germ
cell tumors).
Extraspinal ependymoma[edit]
Extraspinal ependymoma, usually considered to be a glioma (a type of nongerm cell
tumor), may be an unusual form of mature teratoma. [48]

Treatment[edit]
Surgery[edit]
The treatment of choice is complete surgical removal (i.e., complete resection).[49]
[50]
 Teratomas are normally well-encapsulated and noninvasive of surrounding tissues,
hence they are relatively easy to resect from surrounding tissues. Exceptions include
teratomas in the brain, and very large, complex teratomas that have pushed into and
become interlaced with adjacent muscles and other structures.
Prevention of recurrence does not require en bloc resection of surrounding tissues.
Chemotherapy[edit]
For malignant teratomas, usually, surgery is followed by chemotherapy.
Teratomas that are in surgically inaccessible locations, or are very complex, or are likely
to be malignant (due to late discovery and/or treatment) sometimes are treated first with
chemotherapy.[citation needed]
Follow-up[edit]
Although often described as benign, a teratoma does have malignant potential. In a UK
study of 351 infants and children diagnosed with "benign" teratoma reported 227 with
MT, 124 with IT. Five years after surgery, event-free survival was 92.2% and 85.9%,
respectively, and overall survival was 99% and 95.1%. [51] A similar study in Italy reported
on 183 infants and children diagnosed with teratoma. At 10 years after surgery, event-
free and overall survival were 90.4% and 98%, respectively. [52]
Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals
with systemic effects. Some teratomas secrete the "pregnancy hormone" human
chorionic gonadotropin (βhCG), which can be used in clinical practice to monitor the
successful treatment or relapse in patients with a known HCG-secreting teratoma. This
hormone is not recommended as a diagnostic marker, because most teratomas do not
secrete it. Some teratomas secrete thyroxine, in some cases to such a degree that it
can lead to clinical hyperthyroidism in the patient. Of special concern is the secretion
of alpha-fetoprotein (AFP); under some circumstances, AFP can be used as a
diagnostic marker specific for the presence of yolk sac cells within the teratoma. These
cells can develop into a frankly malignant tumor known as yolk sac
tumor or endodermal sinus tumor.
Adequate follow-up requires close observation, involving repeated physical
examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or
βhCG.[53][54]

Epidemiology[edit]

Ovarian tumors by incidence and risk of ovarian cancer, with mature cystic teratoma at bottom and immature
teratoma at right.[55]

Embryonal teratomas most commonly occur in the sacrococcygeal

region; sacrococcygeal teratoma is the single most common tumor found in newborn
humans.
Of teratomas on the skull sutures, about 50% are found in or adjacent to the orbit.
[56]
 Limbal dermoid is a choristoma, not a teratoma.
Teratoma qualifies as a rare disease, but is not extremely rare. Sacrococcygeal
teratoma alone is diagnosed at birth in one out of 40,000 humans. Given the current
human population and birth rate, this equals five per day or 1800 per year. Add to that
number sacrococcygeal teratomas diagnosed later in life, and teratomas in other
locales, and the incidence approaches 10,000 new diagnoses of teratoma per year. [citation
needed]

Other animals[edit]
Ovarian teratomas have been reported in mares,[57] mountain lions,[58][59] and in canines.
[60]
 Teratomas also occur, rarely, in other species. [61]
Use in stem cell research[edit]
Pluripotent stem cells including human induced pluripotent stem cells have a unique
property of being able to generate teratomas when injected in rodents in the research
laboratory.[62] For this reason, the so-called "teratoma assay" is one of the gold-standard
validation assays for pluripotent stem cells. [63] Because differentiated human pluripotent
stem cells are being developed as the basis for numerous regenerative medicine
therapies, there is concern that residual undifferentiated stem cells could lead to
teratoma formation in injected patients, and researchers are working to develop
methods to address this concern.[64]