AUTHOR AND EDITOR INFORMATION

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• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

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Background

Teratomas are tumors comprising more than a single cell type derived from more than one germ layer. A significant degree of confusion has arisen 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). Additionally, teratomas may be monodermal and highly specialized, and, rarely within some mature teratomas, certain elements (most commonly squamous components) may undergo malignant transformation.

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 dermoid and teratoma, terms now more than a century old, remain in general use and often are used interchangeably. The earliest implications were that dermoids were predominantly composed of elements similar to skin and its appendages, while teratomas had no such limits. Dermoids now are recognized as often being trigeminal and containing practically any type of tissue.

For 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 differentiates dermoids from teratomas. This article focuses on mature cystic teratomas, commonly referred to as dermoid cysts.

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 paraxial. The most common location is sacrococcygeal (57%). Because they arise from totipotential cells, they are encountered commonly 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 (see Images 1-2).

Frequency

International

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 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 diagnosed commonly in the prenatal period, and complications may occur in utero or during or after birth. The outcome for fetuses with sacrococcygeal teratomas is much worse than for neonates with this tumor, with a survival rate of 53% in fetuses compared with 85% in neonates in one large series.

Potential complications in utero include polyhydramnios and tumor hemorrhage, which can lead to anemia and nonimmune hydrops fetalis. If significant atrioventricular 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 it is 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. Hydrops and prematurity are the two main factors that contribute to mortality.

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 that included 57 cases of benign teratomas over a 40-year period from a single institution, 5 recurrences were documented. 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 rates 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 have demonstrated that increasing tumor size correlates with increased risk of torsion.

Rupture of a cystic teratoma is rare and may be spontaneous or associated with torsion. It 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 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 rare cases. In these reports, 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 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, mature cystic teratoma of the ovary always is benign, but in approximately 0.1-2% 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 adenocarcinoma.

Testicular teratoma

Testicular teratomas occur in children and adults, but their incidence and natural history contrasts sharply. Pure teratomas are fairly common in children, comprising nearly half of germ cell tumors. They are relatively rare after puberty and constitute only 2-3% of germ cell tumors in this age group. 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.

During and after puberty, all teratomas are regarded as malignant because even mature teratomas (composed of entirely mature histologic elements) can metastasize to retroperitoneal lymph nodes or to other systems. Morbidity is associated with growth of the tumor, which may invade or obstruct local structures and become unresectable. Malignant transformation is significantly more common in testicular teratomas than in their ovarian counterparts, and recurrence risk is around 20% in both mature and immature testicular teratomas.

Mediastinal teratoma

Mature teratomas of the mediastinum, the most common mediastinal germ cell tumor, 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 more commonly are 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 at 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 reported age at diagnosis 32-35 years.
• 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.
• Mediastinal teratomas can be found in any age group but occur most commonly in adults aged 20-40 years.

CLINICAL

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History

• Sacrococcygeal teratoma: Sacrococcygeal teratomas not diagnosed antenatally 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 mature cystic teratomas of the ovaries have been reported at rates of 6-65% in various series. When symptoms are present, they may include abdominal pain, mass or swelling, and abnormal uterine bleeding. 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' studies of mature cystic teratomas of the ovaries. 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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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

• 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

• The workup for cystic teratomas is largely radiographic, and their appearance is similar despite varying locations.
• • If the teratoma is 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 (see Image 3). Ultrasound may reveal mass displacement of the bladder and rectum, with compression of the ureters resulting in hydroureter or hydronephrosis.
  • 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 Mais 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.
  • 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 resectability.
  • 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

• 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 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. A careful histopathologic study of 100 cases of ovarian teratomas found ectodermal structures in 100%, mesodermal structures in 93%, and endodermal structures in 71%.

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 development of hydrops prior to 30 weeks' gestation, these fetuses may benefit from in utero surgery. In most cases, sacrococcygeal teratomas should be resected electively 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 always should 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.
• Mature cystic teratomas of the ovaries may be removed by simple cystectomy rather than salpingo-oophorectomy (see Image 4).
• • Although malignant degeneration is quite rare, 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 counseled appropriately about the risks and benefits of laparoscopy and laparotomy. Ample literature supports laparoscopy as an acceptable alternative approach in resection. Benefits include reductions 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 increased risk of chemical peritonitis (estimated incidence of 0.2%) and increased risk of adhesion formation. The risks of recurrence (4%), as well as malignant degeneration (0.17-2%), should be discussed.
• Testicular teratomas traditionally have been treated by simple or radical orchiectomy. More recently, conservative excision by enucleation also has been recommended for prepubertal teratomas of the testis.
• • Several studies have failed to demonstrate negative sequelae for these testicular tumors. 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, proceeding to orchiectomy is recommended. 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 structures, 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.

FOLLOW-UP

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Complications

• See Mortality/Morbidity.
• For surgical complications, see Surgical Care.

Prognosis

• See Mortality/Morbidity.

Patient Education

• Patients should be informed of the risks of surgery and of the various surgical options, as discussed in Surgical Care.
• For excellent patient education resources, visit eMedicine's Procedures Center. Also, see eMedicine's patient education article Dermoid Cyst Removal.

MISCELLANEOUS

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Special Concerns

• 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.

MULTIMEDIA

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Media file 1:  Mature cystic teratoma of the ovary exhibiting multiple tissue types.
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Media file 2:  Mature cystic teratoma of the ovary with hair, sebaceous material, and thyroid tissue.
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Media file 3:  Large teratomatous epignathus diagnosed by prenatal ultrasound.
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Media type:  Photo

Media file 4:  A 12-cm mature cystic teratoma of the ovary prior to excision.
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Media type:  Photo

REFERENCES

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• Shukla AR, Woodard C, Carr MC, et al. Experience with testis sparing surgery for testicular teratoma. J Urol. Jan 2004;171(1):161-3.
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Article Last Updated: Jun 30, 2006