Cystic Teratoma

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Teratomas are germ cell tumors commonly composed of multiple cell types derived from one or more of the 3 germ layers. 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. This article focuses on mature cystic teratomas, commonly referred to as dermoid cysts. See the images below.

Malignant transformation occurs in 1–3% of mature cystic teratomas (MCTs), usually in postmenopausal women. Transformation to squamous cell carcinoma occurs most commonly (75%), followed by transformation to adenocarcinoma and carcinoid tumors. ^[1]

Sacrococcygeal teratomas may be diagnosed antenatally during routine ultrasounds, fetal anomaly scans, or when the mother presents with clinical symptoms such as size greater than dates or polyhydramnios. ^[2]  Mature cystic teratomas of the ovary are often discovered as incidental findings on physical examination, during radiographic studies, or during abdominal surgery performed for other indications. Testicular teratomas most often present as a painless scrotal mass, except in the case of torsion. Mediastinal teratomas are often asymptomatic.

The treatment of mature teratomas is largely surgical. Patients should be informed of the risks of surgery and of the various surgical options, as discussed in Surgical Care.

For patient education information, see Dermoid Cyst Removal.

Inconsistent nomenclature often confuses discussions of various subtypes of teratomas. The word is derived from the Greek teras, meaning monster, which Virchow coined in the first edition of his book on tumors, published in 1863. ^[3]

In 1831, Leblanc coined the term dermoid cyst in the veterinary literature when he removed a lesion that resembled skin at the base of a horse’s skull, which he called a “kyste dermoid.” ^[4] Both dermoid and teratoma, terms now more than a century old, remain in general use and often are used interchangeably, with various preferences among subspecialties. The earliest implications were that elements similar to skin and its appendages comprised dermoids, while teratomas had no such limits. Dermoids now are recognized as often being trigerminal 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, are essentially devoid of organization; thus, the presence of some degree of organization, a high degree of cellular differentiation, and cystic structure differentiates dermoids from teratomas. ^[3]

Teratomas are made up of a variety of parenchymal cell types representing more than 1 germ layer and often all 3. Arising from totipotential cells, these tumors typically are midline or paraxial. ^[5]

The most common location is sacrococcygeal (57%). Because they arise from totipotential cells, teratomas 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%). ^[6]

Cells differentiate along various germ lines, essentially recapitulating any tissue of the body. Examples include hair, teeth, fat, skin, muscle, and endocrine tissue.

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. ^{[5, 7]}  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. ^[8]

Sacrococcygeal teratomas (SCT) are the most common tumors in newborns, occurring in 1 per 20,000-40,000 births. ^{[5, 9]} A population-based (rather than tertiary referral center) estimate from the United Kingdom found a birth prevalence of 1 per 27,000 live births. ^[10]  A retrospective study of newborns diagnosed with SCT in southern Sweden from 2000 to 2013 found an overall incidence of approximately 1 per 14,000 live births, with overall mortality of 11%. ^[11]

Mature cystic teratomas account for 10-20% of all ovarian neoplasms. They are the most common ovarian germ cell tumor and also the most common ovarian neoplasm in patients younger than 20 years. They are bilateral in 8-14% of cases. ^{[4, 3, 12, 13]}

The incidence of all testicular tumors in men is 2.1-2.5 cases per 100,000 population. 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. ^{[14, 15]}

Benign teratomas of the mediastinum are rare, representing 8% of all tumors of this region. ^[16]

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. ^[6]

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. ^[17]

An increasing number of patients with sacrococcygeal teratomas are diagnosed antenatally. In the series by Gabra et al, this proportion increased from 11% before 1988 to 53% from 1988-2001. Patients presenting later tend to have less obvious external tumors; symptoms of bladder or bowel dysfunction often lead to diagnosis. ^[18]

Cystic teratomas of the ovary can occur in persons of any age, although they are diagnosed most frequently during the reproductive years. The peak incidence in most series is at age 20-40 years. ^[19]

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. ^[20]

Mediastinal teratomas can be found in persons of any age but occur most commonly in adults aged 20-40 years. ^{[16, 21]}

Mature cystic teratomas can result in significant morbidity. Potential complications vary depending on the site of occurrence.

Sacrococcygeal teratomas are commonly diagnosed prenatally, and complications may occur in utero or during or after birth. The outcome after prenatal diagnosis is significantly worse than that in older postnatal surgical series, with survival rates ranging from 54-77%. ^{[2, 22, 23]}

Potential complications in utero include polyhydramnios and tumor hemorrhage, which can lead to anemia and nonimmune hydrops fetalis. If significant arteriovenous 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. ^{[22, 24]}  Makin et al reported that antenatal intervention for the treatment of fetal hydrops did not improve outcomes with neonatal deaths in 6 of 7 cases (86%). ^[2]  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. Ten to twenty-four percent 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. ^{[25, 18, 5]}

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. The overall survival was 95% and morbidity or mortality rates were consistent over the 40-year period of the study. ^[9]

In a more recent series, all 26 patients diagnosed with benign teratomas survived. Seven of 20 patients with long-term follow-up developed neuropathic bladder or bowel disturbances. ^[18]  

Partridge and colleagues studied a series of 45 patients, noting anorectal complications in 29% and urologic complications in 33%. These were associated with both prenatal obstructive findings and therapeutic interventions, as well as Altman classification, perineal reconstruction, and tumor recurrence. ^[26]  A longitudinal cross-sectional follow-up study found that sequelae developing in childhood tended to improve with time, while functional symptoms reported in adulthood were common in the general population and not significantly increased over a control group. ^[27]

In a Dutch study of 47 adults who had been treated for SCT during infancy between 1970 to 1993, urinary incontinence was present in 30% and had a greater reported negative impact than unintentional defecation. Ten patients (21%) reported constipation; a tumor diameter of >10 cm and Altman type I or type II SCT were associated with constipation during adulthood. ^[28]

Complications of ovarian teratomas include the following:

Torsion is by far the most significant cause of morbidity, occurring in –3-11% of cases. Several series have demonstrated that increasing tumor size correlates with increased risk of torsion. ^{[4, 29]}

Rupture of a cystic teratoma is rare and may be spontaneous or associated with torsion. Most series report a rate of less than 1%, ^{[4, 3]}  though Ahan et al reported a rate of 2.5% in their report of 501 patients. ^[19]  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 is usually favorable, but the rupture often results in formation of dense adhesions.

Infection is uncommon and occurs in less than 1-2% of cases. Coliform bacteria are the organisms most commonly implicated. ^{[19, 29]}

Encephalitis associated with antibodies against the N-methyl D-aspartate receptor (NMDAR) has been linked to tumors, especially ovarian mature teratomas. In a series of 400 cases, 335 of them in women, 165  patients (49%) had tumors and all but six were ovarian teratomas. The syndrome is characterized by a viral-like prodrome followed by a multistage progression of symptoms that includes psychosis, memory deficits, seizures, language disintegration, decreased consciousness, dyskinesias, and autonomic instability. Substantial recovery is usually seen with tumor resection and immunotherapy. ^[30]

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. ^{[31, 32]}

In its pure form, mature cystic teratoma of the ovary is always benign, but in approximately 0.2-2% of cases, it may undergo malignant transformation into one of its elements, the majority of which are squamous cell carcinomas. The prognosis for patients with malignant degeneration is generally poor but dependent on stage and degenerated cell type. ^{[4, 33]}

Testicular teratomas occur in children and adults, but their incidence and natural history contrast sharply. Pure teratomas comprise 38% of germ cell tumors in infants and children but only 3% after puberty. In children, they behave as a benign tumor, whereas in adults and adolescents they are known to metastasize. ^{[20, 34]}  With no documented cases of metastasis, morbidity from prepubertal testicular teratomas is largely limited to surgical or postoperative complications.

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. Reported rates of metastasis vary from 29-76%. Morbidity is associated with growth of the tumor, which may invade or obstruct local structures and become unresectable. Approximately 20% of patients relapse during surveillance. ^[20]

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 are often intimately involved with the tumor. ^[35]

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Chad A Hamilton, MD Chief, Gynecologic Oncology Service, Walter Reed National Military Medical Center; Program Director, NCC Fellowship in Gynecologic Oncology

Chad A Hamilton, MD is a member of the following medical societies: Alpha Omega Alpha, Society of Gynecologic Oncology, American College of Obstetricians and Gynecologists

Disclosure: Nothing to disclose.

Margarett C Ellison, MD Consulting Staff, Kaiser Permanente, Los Angeles Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD 

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

from Memorial Sloan-Kettering – Yukio Sonoda, MD Associate Professor, Weill Cornell Medical College; Associate Attending Surgeon, Gynecology Service, Department of Surgery, Memorial Hospital for Cancer and Allied Diseases; Associate Member, Memorial Sloan-Kettering Cancer Center

from Memorial Sloan-Kettering – Yukio Sonoda, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American College of Surgeons, American Medical Association, Society of Gynecologic Oncology, Society of Laparoendoscopic Surgeons, AAGL, American Society of Clinical Oncology, International Gynecologic Cancer Society, Japanese Medical Society of America, Korean American Medical Assocation

Disclosure: Nothing to disclose.

Lodovico Balducci, MD Professor, Oncology Fellowship Director, Department of Internal Medicine, Division of Adult Oncology, H Lee Moffitt Cancer Center and Research Institute, University of South Florida Morsani College of Medicine

Lodovico Balducci, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American College of Physicians, American Geriatrics Society, American Society of Hematology, New York Academy of Sciences, American Society of Clinical Oncology, Southern Society for Clinical Investigation, International Society for Experimental Hematology, American Federation for Clinical Research, American Society of Breast Disease

Disclosure: Nothing to disclose.

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