|
INTRODUCTION |
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Background: Teratomas are
tumors in which more than a single cell type is derived from more than one germ
layer. There has been a significant degree of confusion regarding nomenclature
for the various subtypes of teratomas. The word itself is derived from the Greek
word teraton, meaning monster, and was used initially by Virchow in the
first edition of his book on tumors, which was published in 1863. Teratomas
range from benign, well-differentiated (mature) cystic lesions to those that are
solid and malignant (immature). Monodermal and highly specialized teratomas, as
well as mature teratomas with malignant transformation also occur.
The term dermoid cyst was coined in the veterinary literature in 1831 by
Leblanc when he removed a lesion that resembled skin at the base of a horse’s
skull, which he called a kyste dermoid. Both terms, now more than a century old,
still are in general use and often are used interchangeably. The earliest
implications were that dermoids were composed predominantly of elements similar
to skin and its appendages, while teratomas had no such limits. It is now
recognized that dermoids are indeed often trigeminal and may contain practically
any type of tissue. In those who continue to make a distinction, dermoids are
tumors that maintain rather orderly arrangements, with well-differentiated
ectodermal and mesodermal tissues surrounding endodermal components. Teratomas,
specifically solid teratomas, essentially are devoid of organization; thus, the
presence of some degree of organization, a high degree of cellular
differentiation, and cystic structure differentiate dermoids from teratomas.
This article focuses onmaturecystic teratomas, commonly referred to as dermoid
cysts.
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Pathophysiology: Teratomas are made up of a variety of
parenchymal cell types representative of more than a single germ layer, usually
all 3. Arising from totipotential cells, these tumors typically are midline or
para-axial. The most common location is sacrococcygeal (57%). Because they arise
from totipotential cells, they are commonly encountered in the gonads (29%). By
far the most common gonadal location is the ovary, although they also occur
somewhat less frequently in the testes. Cystic teratomas occasionally occur in
sequestered midline embryonic cell rests and can be mediastinal (7%),
retroperitoneal (4%), cervical (3%), and intracranial (3%). Cells differentiate
along various germ lines, essentially recapitulating any tissue of the body.
Examples include hair, teeth, fat, skin, muscle, and endocrine tissue.
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Frequency:
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- Internationally: Sacrococcygeal teratomas are the most
common tumors in newborns, occurring in 1 per 20,000-40,000 births.
Mature cystic teratomas account for 10-20% of all ovarian neoplasms. Not
only are they the most common ovarian germ cell tumor but also the most common
ovarian neoplasm in patients younger than 20 years. They are bilateral in
8-15% of cases.
The incidence of all testicular tumors in men is 2.1-2.5 per 100,000. Germ
cell tumors represent 95% of testicular tumors after puberty, but pure benign
teratomas of the testis are rare, accounting for only 3-5% of the germ cell
tumors. The incidence of all testicular tumors in prepubertal boys is 0.5-2
per 100,000, with mature teratomas accounting for 14-27% of these tumors. It
is the second most common germ cell tumor in this population.
Benign teratomas of the mediastinum are rare, representing 8% of all tumors
of this region.
Mortality/Morbidity: Mature cystic
teratomas can result in significant morbidity. Potential complications vary
depending on the site of occurrence.
Sacrococcygeal teratoma
Sacrococcygeal teratomas are commonly diagnosed in the prenatal period, and
complications may occur in utero, or during or after birth.
Potential complications in utero include polyhydramnios and tumor hemorrhage,
which can lead to anemia and nonimmune hydrops fetalis. If significant
atrioventricular (A-V) shunting occurs within the tumor, hydrops may result from
high-output cardiac failure. Development of hydrops is an ominous sign. If it
develops after 30 weeks?gestation, the mortality rate is 25%. If recognized,
delivery is recommended as soon as lung maturity is documented. Development of
hydrops before 30 weeks?gestation has an abysmal prognosis, with a 93% mortality
rate.
Postpartum, morbidity associated with sacrococcygeal teratomas is
attributable to associated congenital anomalies, mass effects of the tumor,
recurrence, and intraoperative and postoperative complications. Approximately
10% of sacrococcygeal teratomas are associated with other congenital anomalies,
primarily defects of the hindgut and cloacal region, which exceeds the baseline
rate of 2.5% expected in the general population.
In one larger series including 57 cases of benign teratomas over a 40-year
period from a single institution, there were 5 recurrences. Only one of the
patients who experienced recurrence did not undergo a coccygectomy, and one
patient who was thought to have a benign tumor with immature elements was found
to have embryonal carcinoma after the third excision. In this same series, 3
patients had postoperative wound infections and one patient had postoperative
pneumonia. Three patients died in this series. One died with group B sepsis
prior to surgery, one died of disseminated intravascular coagulation and sepsis
2 days after surgery, and one died of massive intraabdominal hemorrhage thought
to be unrelated to the surgery. No significant change in morbidity or mortality
could be identified over the 40-year period of the study.
Ovarian teratoma
Complications of ovarian teratomas include torsion, rupture, infection,
hemolytic anemia, and malignant degeneration.
Torsion is by far the most significant cause of morbidity, occurring in
3.2-16% of cases. Several series demonstrate that increasing tumor size
correlates with increased risk of torsion.
Rupture of a cystic teratoma may be spontaneous or associated with torsion
and occurs in approximately 1-4% of cases. Rupture may occur suddenly, leading
to shock or hemorrhage with acute chemical peritonitis. Chronic leakage also may
occur, with resultant granulomatous peritonitis. Prognosis after rupture usually
is favorable, but the rupture often results in the formation of dense adhesive
disease.
Infection is uncommon and occurs in only 1% of cases. Coliform bacteria are
the organisms most commonly implicated.
Autoimmune hemolytic anemia has been associated with mature cystic teratomas.
In several series, removal of the tumor resulted in complete resolution of
symptoms. Theories behind the pathogenetic mechanism include (1) tumor
substances that are antigenically different from the host and produce an
antibody response within the host that cross reacts with native red blood cells,
(2) antibody production by the tumor directed against host red blood cells, and
(3) coating of the red blood cells by tumor substance that changes the red blood
cell antigenicity. In this context, radiologic imaging of the pelvis may be
indicated in cases of refractory hemolytic anemia.
In its pure form, the mature cystic teratoma of the ovary always is benign,
but in approximately 2% of cases, it may undergo malignant transformation into
one of its elements. The prognosis for patients with malignant degeneration is
dismal, with 5-year survival rates reported in the range of 15-31%. The
prognosis appears to be somewhat better if the malignant element is squamous
rather than an adenocarcinoma.
Testicular teratoma
Testicular teratomas occur in children and adults. In children, they behave
as a benign tumor, whereas in adults and adolescents they invariably are
malignant neoplasms.
Childhood testicular teratomas are uniformly benign, with no documented cases
of retroperitoneal or lung metastasis in differentiated lesions. Most morbidity
is a result of surgical or postoperative complications, such as hemorrhage or
infection. The mortality rate is less than 1 per million.
Pure teratomas of the testis are rare. However, during and after puberty,
even mature teratomas (composed of entirely mature histologic elements) can
metastasize to the retroperitoneal lymph nodes or systemically regardless of
their histologic appearance. Morbidity is associated with tumor growth, which
may invade or obstruct local structures and become unresectable. Malignant
transformation is significantly higher in testicular teratomas compared to their
ovarian counterparts, and recurrence risk is around 20% in both mature and
immature testicular teratomas.
Mediastinal teratoma
Mature teratomas of the mediastinum are benign lesions. They do not have the
metastatic potential observed in testicular teratoma and are cured by surgical
resection alone. Because of their anatomic location, intraoperative and
postoperative complications are the only significant source of morbidity, as
other intrathoracic structures often are intimately involved with the tumor.
Sex: Sacrococcygeal teratomas are much more common in
females than in males, occurring in a female-to-male ratio of approximately
3-4:1. Most sources report no sex predilection for mediastinal teratomas. Others
document a marked male or marked female predominance. Excluding testicular
teratomas, 75-80% of teratomas occur in girls.
Age: The presenting location of teratomas correlates with
age.
- In infancy and early childhood, the most frequent location is extragonadal,
whereas teratomas presenting after childhood are more commonly located in the
gonads.
- Although some sacrococcygeal teratomas are diagnosed antenatally or in
early childhood, most are diagnosed neonatally, usually on the first day of
life.
- Cystic teratomas of the ovary can occur in persons of any age, although
they are far more common during the reproductive years. Approximately 85% of
mature cystic teratomas occur in women aged 16-55 years, with mean age at
diagnosis reported of 32-35 years.
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- Testicular teratomas may occur at any age but are more common in infants
and children. In adults, pure testicular teratomas are rare, constituting 2-3%
of germ cell tumors.
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- Mediastinal teratomas can be found in any age group but most commonly
occur in adults aged 20-40 years.
|
CLINICAL |
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History:
- Sacrococcygeal teratoma: In those not diagnosed antenatally,
sacrococcygeal teratomas present in 2 patterns. The most common pattern is in
neonates, who present with a large, predominantly benign tumor protruding from
the sacral area that is noted prenatally or at the time of delivery. Less
commonly, the newborn may exhibit only asymmetry of the buttocks or present
when aged 1 month to 4 years with a presacral tumor that may extend into the
pelvis. The latter group is at higher risk for malignancy.
- Ovarian teratoma: Mature cystic teratomas of the ovary often are
discovered as incidental findings on physical examination, during radiographic
studies, or during abdominal surgery performed for other indications.
Asymptomatic ovarian mature cystic teratomas are reported at a rate of 6-65%
in various series. When symptoms are present, they usually consist of
abdominal pain (47.6%), abdominal mass or swelling (15.4%), and abnormal
uterine bleeding (15.1%). Bladder symptoms, gastrointestinal disturbances, and
back pain are less frequent. When abdominal pain is present, it usually is
constant and ranges from slight to moderate in intensity. Torsion and acute
rupture commonly are associated with severe pain. Hormonal production is
thought to account for cases of abnormal uterine bleeding, but histologic
examination has not provided evidence of this theory.
- Testicular teratomas most often present as a painless scrotal mass, except
in the case of torsion. The masses are firm or hard in 83% of cases. Most are
not tender and do not transilluminate. Testicular pain and scrotal swelling
occasionally are reported with teratomas, but this is nonspecific and simply
indicates torsion until proven otherwise. Hydrocele frequently is associated
with teratoma in childhood. On examination, the testis is diffusely enlarged,
rather than nodular, although a discreet nodule in the upper or lower pole
sometimes can be appreciated.
- Mediastinal teratomas often are asymptomatic. When symptoms are present,
they relate to mechanical effects including chest pain, cough, dyspnea, or
symptoms related to recurrent pneumonitis. Many patients present with
respiratory findings, and the pathognomonic finding of trichoptysis, or cough
productive of hair or sebaceous material, may result if a communication
develops between the mass and the tracheobronchial tree. Other serious
presentations are superior vena cava syndrome or lipoid pneumonia. Mediastinal
teratomas occasionally are discovered incidentally on chest radiograph.
Physical: See
History
Causes: The existence of teratomas has been recognized for
centuries, during which time their origin was a matter of speculation and
debate. Common early beliefs blamed ingestion of teeth and hair, as well as
curses from witches, nightmares, or even adultery with the devil. The
parthenogenic theory, which suggests an origin from the primordial germ cells,
is now the most widely accepted. This theory is bolstered by the anatomic
distribution of the tumors along lines of migration of the primordial germ cells
from the yolk sac to the primitive gonads. Additional support came from Linder
and associates while studying ovarian mature cystic teratomas. They used
sophisticated cytogenetic techniques to demonstrate that these tumors are of
germ cell origin and arise from a single germ cell after the first meiotic
division.
|
DIFFERENTIALS |
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Adnexal Tumors
[Benign Lesions of the Ovaries]
Borderline Ovarian Cancer
Ectopic Pregnancy
Endometrial Carcinoma
Endometriosis
Extragonadal Germ Cell
Tumors
Fallopian Tube and Broad
Ligament Disorders
Germ Cell Tumors
Granulosa-theca Cell Tumors
Hydrocele
Lymphoma, Mediastinal
Lymphomas, Endocrine,
Mesenchymal, and Other Rare Tumors of the Mediastinum
Malignant Lesions of the
Fallopian Tube and Broad Ligament
Malignant Lesions of the
Ovaries
Mediastinal Cysts
Neurogenic Tumors of the
Mediastinum
Ovarian Cancer
Ovarian Cysts
Ovarian Dysgerminomas
Peritoneal Cancer
Pilonidal Disease
Rectal Prolapse
Spinal Malformation
Testicular Choriocarcinoma
Testicular Seminoma
Testicular Torsion
Testicular Trauma
Testicular Tumors:
Nonseminomatous
Thymic Tumors
Thymoma
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Other Problems to be Considered:
Sacrococcygeal teratomas should be differentiated from neural tube defects,
specifically meningoceles or meningomyeloceles. Also included in the
differential are epidermoid cysts, anal duct or pilonidal cysts, rectal
abscesses, lymphangiomas, imperforate anus, and rectal prolapse.
Ovarian cystic teratomas should be differentiated from other benign or malignant
ovarian neoplasms, endometriomas, tuboovarian abscesses, pedunculated uterine
fibroids, hydrosalpinxes, ectopic pregnancies, pelvic kidneys, and peritoneal
cysts.
Testicular teratomas should be differentiated from juvenile granulosa cell
tumors, cystic dysplasia of the rete testes, testicular cystic lymphangioma, and
simple testicular cysts.
Mediastinal teratomas should be differentiated from other mediastinal masses,
including neurogenic tumors (20%), thymomas (19%), primary cysts (18%),
lymphomas (13%), and germ cell tumors (10%). Other less common mediastinal
masses include primary carcinomas, mesenchymal tumors, endocrine tumors, giant
lymph node hyperplasia, chondromas, and extramedullary hematopoiesis.
|
WORKUP |
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Lab Studies:
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- Elevated serum alpha-fetoprotein (AFP) and beta-human chorionic
gonadotropin (HCG) levels may be indicative of malignancy, as these values are
within reference ranges in most patients with benign teratomas.
Imaging Studies:
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- The workup for cystic teratomas is largely radiographic, and their
appearance is similar despite varying locations.
- If recognized in utero, the fetus should undergo serial ultrasound
surveillance for development of fetal hydrops. In the case of sacrococcygeal
teratomas, an ultrasound examination may demonstrate cystic components and
extension of the tumor into the pelvis or abdomen. Mass displacement of the
bladder and rectum, with compression of the ureters resulting in hydroureter
or hydronephrosis, may be revealed.
- Computed tomography (CT) scanning of the abdomen and pelvis before
surgical exploration can further delineate sacrococcygeal tumor from normal
anatomic features.
- Similarly, ultrasonography with adjunctive CT scanning is useful in
imaging suspected ovarian teratomas and may detect liver and retroperitoneal
lymph node involvement in malignant cases. Ultrasonic findings ascribed to
teratomas include shadowing echo densities, regionally bright echoes,
hyperechoic lines and dots, and fluid-fluid levels. In a study by Valerio et
al, transvaginal ultrasonography had a sensitivity and specificity of 84.6%
and 98.2%, respectively, for differentiating cystic teratoma from other
ovarian masses. In another trial, Patel et al demonstrated a 98% positive
predictive value and 85% sensitivity using ultrasound to diagnose and
identify cystic teratomas.
- CT scan usually reveals the complex appearance of ovarian teratomas,
with dividing septa, internal debris, variable attenuation, and distinct
calcification.
- Magnetic resonance imaging (MRI) can sufficiently differentiate lipid
density from other fluid and blood and may be another useful adjunct for
diagnosis of ovarian teratomas, with an accuracy of 99% (Scoutt, 1994).
- In the case of a suspected mediastinal teratoma, anterior-posterior and
lateral chest radiographs provide important information as to size and
location of the mass.
- CT scan and/or MRI also are invaluable in delineating the boundaries of
mediastinal masses, potential vascular involvement, and respectability.
- Echocardiography can be utilized to delineate physiologic effects of
mediastinal masses, such as tamponade or pulmonary stenosis, and may be used
to guide needle biopsy.
Procedures:
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- Fine-needle aspiration or core biopsy can be used to differentiate benign
from malignant mediastinal masses in 90% of cases.
Histologic Findings: In cystic teratomas, the outside of the
tumor wall usually is lined with native tissue. The cavity of the cyst often is
lined with keratinized squamous epithelium and usually contains abundant
sebaceous and sweat glands. Hair and other dermal appendages usually are
present. Occasionally, the cyst wall is lined with bronchial or gastrointestinal
epithelium. Foreign body giant cell reactions may be seen in various parts of
the tumor and may, in the case of intraperitoneal teratomas, lead to the
formation of extensive adhesions if the tumor contents are spilled. Ectodermal
tissue encountered may include brain, glia, neural tissue, retina, choroids, and
ganglia. Mesodermal tissue is represented by bone, cartilage, smooth muscle, and
fibrous tissue.
One report described an asymptomatic 11-cm ovarian dermoid cyst that
contained a mandible with 7 teeth. Representative endodermal tissues include
gastrointestinal, bronchial, thyroid, and salivary gland tissue. Representative
proportions of various germ cell tissue in a careful histopathologic study of
100 cases of ovarian teratomas found ectodermal structures in 100%, mesodermal
structures in 93%, and endodermal structures in 71% of cases.
Staging: Sacrococcygeal teratomas are the only teratomas
with a widely accepted staging or classification system. In a study of 405
patients treated by members of the Surgical Section of the American Academy of
Pediatrics, Altman and associates report the following system.
- Type I tumors are predominantly external, attached to the coccyx, and may
have a small presacral component (45.8%). No metastases were associated with
this group.
- Type II tumors have both an external mass and significant presacral pelvic
extension (34%) and have a 6% metastases rate.
- Type III tumors are visible externally, but the predominant mass is pelvic
and intraabdominal (8.6%). A 20% rate of metastases was found in this group.
- Type IV lesions are not visible externally but are entirely presacral
(9.6%) and have an 8% metastases rate.
|
TREATMENT |
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Surgical Care: The treatment of mature
teratomas is largely surgical.
- Sacrococcygeal teratomas diagnosed prenatally should be monitored closely.
- In fetuses with tumors larger than 5 cm, cesarean delivery should be
considered to prevent dystocia or tumor rupture. Because of the poor
prognosis associated with the development of hydrops prior to 30
weeks?gestation, these fetuses may benefit from in utero surgery. In most
cases, sacrococcygeal teratomas should be electively resected in the first
week of life since long delays may be associated with a higher rate of
malignancy.
- Complete excision should be done through a chevron-shaped buttock
incision, with careful attention to the preservation of the muscles of the
rectal sphincter. The coccyx should always be resected with the tumor, as
failure to do so results in a 35-40% recurrence rate. Hemorrhage from the
middle sacral vessels and hypogastric arteries is the most common
complication.
- Ovarian mature cystic teratomas should be removed by simple cystectomy,
rather than salpingo-oophorectomy.
- Although there is only a 1% rate of malignant degeneration, the cyst
should be removed in its entirety, and if immature elements are found, the
patient should undergo a standard staging procedure.
- The patient should be appropriately counseled about the risks and
benefits of laparoscopy and laparotomy. Ample literature supports
laparoscopy as an acceptable alternative approach in resection. Benefits
include a reduction in postoperative pain, blood loss, hospital stay, and
total cost. Risks include prolonged operative time, increased operating room
costs, and potential need for a prompt second staging procedure if an
unexpected malignancy is revealed. Some studies have found an increased
intraoperative spillage rate with laparoscopy, while others have not.
Spillage is associated with an increased risk of chemical peritonitis
(estimated incidence of .2%) and increased risk of adhesion formation. The
risks of recurrence (4%), as well as malignant degeneration (.17-2%), should
be discussed, as well.
- Testicular teratomas traditionally have been treated by simple or radical
orchiectomy. More recently, conservative excision by enucleation has also been
recommended for prepubertal teratomas of the testis.
- Several studies have failed to demonstrate negative sequelae for these
testicular tumors. Of note, the longest follow-up to date is 96 months.
Patients should be counseled regarding the risks of inadequate sampling,
incorrect diagnosis by frozen section, tumor spillage and seeding, and
unidentified microinvasive disease.
- The risk of malignancy increases with maturation of the testes, and this
is a significant concern in children at or near puberty. In this group,
areas of normal surrounding testicular tissue should be excised and sent for
frozen section. If frozen section reveals areas of maturity, it is
recommended to proceed to orchiectomy. Enucleation or partial orchiectomy
for teratoma in pubertal or adult males is not recommended.
- Mature teratomas of the mediastinum should be completely surgically
resected. The tumor may be adherent to surrounding structure necessitating
resection of the pericardium pleura or lung. When complete resection is
achieved, it results in excellent long-term cure rates with little chance of
recurrence.
|
MISCELLANEOUS |
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Special Concerns:
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- Benign cystic teratomas of the ovary found during pregnancy present the
unique problem of weighing the risks of surgery and anesthesia versus the risk
of the persistent adnexal mass.
- In a large study of benign cystic teratomas during pregnancy, torsion
occurred in 19%, while tumor rupture and obstruction of labor occurred in 3%
and 14% of patients, respectively. An additional 22% of women required
surgery in the puerperium for torsion, rupture, or infection of the mass.
Furthermore, malignancy is reported in 5% of adnexal masses during
pregnancy. One study found an increased risk of spontaneous abortion
(relative risk 2.0) when surgery was conducted during the first or second
trimester, while another study found a slightly increased risk of preterm
delivery. Significantly, in a study of 54 patients, Hess and others
demonstrated that women who underwent elective removal of an adnexal mass
during pregnancy had less morbidity than the 15 who underwent emergency
laparotomy for a symptomatic mass in the emergency setting.
- The authors recommend elective removal of any adnexal mass larger than 6
cm that persists beyond 16 weeks?gestation to avoid the potential risks of
surgical emergency. Laparoscopic removal also has been demonstrated an
equally safe alternative to laparotomy in the late first or second
trimester.
|
PICTURES |
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Caption: Picture 1.
Ovarian mature cystic teratoma exhibiting multiple tissue types |
|
Picture Type: Photo |
Caption: Picture 2. A 12-cm ovarian
mature cystic teratoma prior to excision |
|
Picture Type: Photo |
Caption: Picture 3. Ovarian mature
cystic teratoma with hair, sebaceous material, and thyroid tissue |
|
Picture Type: Photo |
Caption: Picture 4. Large teratomatous
epignathus diagnosed by prenatal ultrasound |
|
Picture Type: Photo |
|
BIBLIOGRAPHY |
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