Sacrococcygeal teratoma

INTRODUCTION — Germ cell tumors (GCTs) that arise outside the testes or the ovaries are classified as extragonadal. Extragonadal GCTs typically arise in midline locations, and specific sites vary with age. In adults, the most common sites are the anterior mediastinum, retroperitoneum, and the pineal and suprasellar regions. In infants and young children, sacrococcygeal teratomas (SCTs) are the most common GCTs.

SCTs are discussed here. Extragonadal GCTs arising in the central nervous system and in the mediastinum and retroperitoneum are discussed elsewhere. (See "Intracranial germ cell tumors" and "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)

EPIDEMIOLOGY — SCT is the most common germ cell tumor (GCT) of childhood. In the pediatric population, SCTs account for 40 percent of all GCTs and up to 78 percent of all extragonadal GCTs. Rarely, SCTs may present in adulthood [1,2].

SCT is the most frequently recognized fetal neoplasm, with an estimated incidence of approximately 1 in 27,000 [3]. SCTs are more common in females than males, with a 3 to 4:1 ratio [4,5]. SCTs with malignant elements generally are not seen in infants. The incidence of malignant elements within SCTs increases with postnatal age.

PATHOLOGY

Histology — Teratomas often are comprised of cells that represent all three germ cell layers. They have solid, cystic, or mixed components. Unlike teratomas in other locations, SCTs often do not have a capsule or pseudocapsule, which contributes to the difficulty in achieving a complete resection.

As teratomas, SCTs can include mature, immature, and malignant tissues:

●Mature teratomas – Mature teratomas consist of fully differentiated tissues from various somatic sites. These tissues may be small islands of cells mixed together, or they can include fully functional glandular structures such as pancreatic Langerhans cells or sebaceous glands. Fully developed bone, hair, and teeth have been found in mature teratomas.

●Immature teratomas – Immature teratomas include at least a small fraction of cells that are comprised of embryonal components or incompletely differentiated tissue structures. Primitive neuroectodermal features, such as primitive neural tubes and immature rosettes, are common. The Gonzalez-Crussi grading system has been used to describe the amount of immature tissue within the tumor: Grade 0: mature teratoma only; Grade 1: <10 percent immature tissue; Grade 2: 10 to 50 percent immature tissue; and Grade 3: >50 percent immature tissue [6]. Other grading systems have also been described [7-9].

●Malignant teratomas – SCTs that contain any malignant elements are considered malignant. Between 11 and 35 percent of postnatal SCTs are malignant, and many of these will have elevated tumor markers [4,10,11]. The most common malignant element is a yolk sac component, which produces alpha-fetoprotein (AFP) [4,9,12]. Other malignant elements can include embryonal carcinoma and primitive neuroectodermal tumor (PNET).

Microfoci of malignant elements can be missed on pathologic sectioning. Therefore, screening with AFP and beta human chorionic gonadotropin (beta-hCG) is part of the initial evaluation of patients with SCT. (See 'Prenatal detection' below.)

Genetics — No consistent genetic changes have been identified in mature and immature teratomas [6]. Both gonadal and extragonadal germ cell tumors (GCTs) of infancy frequently have gain of chromosomes 1q and 20q, as well as loss of chromosomes 1p and 6q. By contrast, postpubertal malignant GCTs are associated with the isochromosome 12p abnormality [6,13,14]. (See "Extragonadal germ cell tumors involving the mediastinum and retroperitoneum".)

CLINICAL PRESENTATION — SCT generally presents either in utero, as a mass extending off the caudal end of the fetus, or as a tumor of infancy that may be asymptomatic or present with signs of obstruction of the rectum or bladder [15,16]. A small number of children present with weakness, pain, or paralysis [17].

The Altman Classification describes the extent to which a tumor is external and/or internal (figure 1). Type I tumors are primarily external, while type IV lesions are completely internal. Type I and II tumors are the most obvious on prenatal ultrasound and clinical examination. In the United Kingdom Children's Cancer Study Group (UKCCSG) experience with 37 SCTs, Altman types I, II, III, and IV were present in 62, 14, 19, and 6 percent of cases, respectively [7].

Type IV tumors typically are found later in infancy and early childhood, compared with tumors with an external component (types I, II, and III). Type IV SCTs can present with obstipation/constipation, abdominal pain, or a palpable mass. Malignant elements are more frequent in type IV SCTs, with an incidence of 38 percent in one series [18].

PRENATAL DETECTION — Prenatal diagnosis typically occurs during the second trimester during routine sonography; first-trimester diagnosis has also been reported [19-22]. Most SCTs diagnosed in utero are Altman type I or II [19].

Diagnosis — Sonography usually demonstrates a mass near the distal spine (picture 1 and picture 2). The majority of prenatally diagnosed SCTs are either solid or mixed cystic and solid; calcifications are often present. Associated structural abnormalities may include bladder outlet obstruction and hydronephrosis, rectal stenosis or atresia, and cardiomegaly secondary to vascular shunting and high-output cardiac failure. (See 'Evaluation and monitoring' below.)

Fetal magnetic resonance imaging (MRI) is recommended where available. Compared with sonography, MRI more accurately characterizes the intrapelvic and abdominal extent of the tumor and compression of adjacent organs (picture 3) [23-25]. This information can help in prenatal counseling and preoperative planning for surgical resection. (See 'Perinatal management' below.)

The most important differential diagnosis of an exophytic cystic sacral mass in the fetus is a distal neural tube defect (myelomeningocele or myelocystocele) [19,26-28]. A neural tube defect is diagnosed when the spinal elements are splayed posteriorly and there is a meningocele or meningomyelocele. SCTs always have a portion in close proximity to the coccyx; they may impinge on the sacrum, but the mass effect is usually presacral rather than posterior, as a neural tube defect would be. Both entities can be associated with elevated maternal and amniotic alpha-fetoprotein (AFP) levels. MRI can be helpful when the diagnosis is unclear by ultrasound [28].

Evaluation and monitoring — Serial ultrasound evaluation of the fetus, placenta, and tumor over the course of the gestation is an important component in the overall treatment plan. The major goal is to identify fetuses at increased risk of fetal demise because of hydrops (ie, high-output cardiac failure due to the vascularity and size of the mass) and intervene as appropriate. (See "Nonimmune hydrops fetalis".)

Tumor size should be measured at each ultrasound examination, and solid portions of the tumor should be interrogated with Doppler ultrasound to assess vascular flow. Rapidly enlarging tumors and tumors that are solid, in particular, create a vascular steal phenomenon, which places the fetus at increased risk of developing hydropic changes [29,30]. Large lesions (>10 cm), especially vascular ones, are associated with a high perinatal mortality rate. Relatively cystic lesions with absent or mild vascularity tend to display slow growth and have a favorable outcome, even when large (>10 cm) [31]. Amniotic fluid volume and placental thickness should also be evaluated, as polyhydramnios and placental thickening are markers for hydrops, and oligohydramnios can result from bladder obstruction due to the SCT.

The frequency of ultrasound examinations depends on the composition of the tumor (ie, cystic or solid), its vascularity, and any associated findings; follow-up imaging may be as often as twice per week for high-risk tumors, or as infrequently as every two weeks for small or predominantly cystic lesions.

Fetal echocardiography is recommended in fetuses with predominantly solid and/or vascular tumors. Echocardiography is used to identify a high-output cardiac state, which precedes the onset of hydrops [32]. A fetal cardiac profile consisting of assessment of the cardiothoracic ratio, cardiac dimension z scores, combined ventricular output, and valvular regurgitation can be used to identify fetuses with poor prognosis [33].

Prognosis — Imaging characteristics, particularly tumor volume, may provide prognostic information [30,34-36]. For example, tumor-volume-to-fetal-weight ratio (TFR) >0.12 on ultrasound before 24 weeks of gestation is a poor prognostic sign [15,30,34,35,37]. In a single-center retrospective study, TFR >0.12 on ultrasound before 24 weeks of gestation was associated with 4.7-fold increase in risk of poor prognosis (hydrops, perinatal death, need for fetal intervention), and a TFR ≥0.11 before 32 weeks was associated with a 6.2-fold increase [35]. In another study, a solid-tumor-volume-to-head-volume ratio >1 was associated with a perinatal mortality rate of 61 percent due to high-output failure and hydrops [30].

A 2023 meta-analysis of 12 studies comprising 447 prenatally diagnosed SCT cases provided information on characteristics associated with a poor outcome (defined as pregnancy termination, fetal death, or neonatal death) [38]. Approximately one-third of cases had a poor outcome; of these, approximately 12 percent were pregnancy terminations, 7 percent were fetal deaths, and 13 percent were neonatal deaths. The frequency of poor outcome with versus without the characteristic was as follows:

●Solid tumor morphology (69 versus 11 percent; OR 20.0, 95% CI 7.9-50.4)

●Fetal hydrops (66 versus 18 percent; OR 9.4, 95% CI 4.0-22.1)

●Cardiomegaly (60 versus 13 percent; OR 7.3, 95% CI 1.9-28.3)

●Hypervascular tumor (55 versus 13 percent; OR 6.2, 95% CI 2.3-16.8)

●Placentomegaly (76 versus 43 percent; OR 4.1, 95% CI 1.6-10.4)

Tumor volume to fetal weight ratio (TFR) >0.12 before 24 weeks of gestation was also predictive of a poor outcome (sensitivity 92 to 100 percent, specificity 76 to 83 percent). Altman type I/II versus type III/IV was not a statistically significant risk factor for poor outcome (24 versus 17 percent; OR 1.3, 95% CI 0.4-4.6).

Other findings included that the mean gestational age at birth in ongoing pregnancies was 32.5 weeks and that perinatal death was mostly due to tumor hemorrhage with hemodynamic failure. The relationship between mode of delivery and outcome was not analyzed, but most live births were by planned cesarean.

A systematic review of 18 studies comprising 420 pregnancies complicated by SCT published in 2015 reported additional findings:

●Survival by Altman type: Type I (78 percent), Type II (70 percent), Type III (86 percent), Type IV (80 percent)

●Fifty-two percent of survivors were delivered at <34 weeks of gestation

Perinatal management — Prenatal diagnosis and close monitoring have improved outcomes for fetal SCT, but overall perinatal mortality remains high [39]. Estimates of perinatal mortality for prenatally diagnosed SCT range from 25 to 50 percent when cases of pregnancy termination, intrauterine death, and neonatal death are included [19,40]. Potential perinatal complications include preterm labor, spontaneous tumor hemorrhage or rupture [41], and maternal Mirror syndrome (maternal edema and hypertension mirroring fetal hydrops). (See "Nonimmune hydrops fetalis", section on 'Mirror syndrome'.)

In utero interventions are generally only temporizing measures to decrease the impact of the parasitic mass on the fetal cardiovascular system, allowing the fetus to recover in utero and continue to grow and mature. A definitive surgical procedure is typically required after the child's birth. For some high-risk SCT fetuses, in utero open fetal surgery is an option at specialized centers. Although criteria for open fetal surgery vary across centers, most include fetuses with high-risk SCT and hydrops developing at a gestational age earlier than appropriate for delivery and neonatal care (eg, 28 to 32 weeks gestation). Contraindications to open fetal surgery include type III or IV Altman-type tumors, severe placentomegaly, cervical shortening, and maternal medical issues [39]. Minimally invasive in utero approaches for management of the hydropic fetus with SCT include laser ablation [42,43], radiofrequency ablation [44,45], bladder drainage for obstructive uropathy [19,46], and cyst aspiration [47]. In a 2014 systematic review, overall perinatal survival with open fetal surgery was 50 percent (6 out of 12) [48]. For minimally invasive procedures, overall perinatal survival was 44 percent (14 out of 32); 30 percent of hydropic fetuses survived (6 out of 20) and 67 percent (8 out of 12) of fetuses without obvious hydrops survived. Mean gestational age at birth for the entire cohort was 30 weeks. Minimally invasive procedures resulting in tumor necrosis enabled performance of a lower-segment uterine incision rather than a classical incision during cesarean delivery.

In high-risk SCT fetuses that are not candidates for in utero intervention, the third trimester can be unpredictable, even with close monitoring. In selected high-risk SCT fetuses, early delivery and ex utero surgery are an option, as advocated by investigators at the Center for Fetal Diagnosis and Treatment at Children's Hospital of Philadelphia [39]. They suggest cesarean delivery, using an ex utero intrapartum therapy (EXIT) procedure when possible, for high-risk SCT after 27 to 28 weeks. High-risk SCTs are those with fetal high-output cardiac failure, tumor hemorrhage, nonreassuring fetal testing (biophysical profile, fetal heart rate tracing, abnormal Dopplers), or impending preterm labor due to polyhydramnios and/or tumor size. In EXIT, the fetus is partially delivered and intubated without clamping the umbilical cord; uteroplacental blood flow and gas exchange are maintained by using inhalational agents to provide uterine relaxation and amnioinfusion to maintain uterine volume. This provides time for debulking the SCT prior to complete delivery of the infant, thereby interrupting the vascular steal that is the basis for high-output cardiac failure.

Fetuses with low-risk SCT are typically delivered by cesarean after 36 weeks of gestation [39]. Fetuses with small tumors (<5 cm) can be delivered vaginally, but the majority of tumors are sufficiently large to necessitate cesarean delivery [49].

POSTNATAL EVALUATION — If fetal MRI was not performed antenatally, computed tomography (CT) or MRI of the primary site is commonly done after birth to assess the extent of internal tumor. Staging should include a CT of the chest and bone scan.

Serum levels of alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (beta-hCG) should be assessed at diagnosis to look for the presence of malignant components in the tumor. Because these tumors generally present at birth or early in infancy, interpretation of an elevated AFP can be difficult and must consider the age of the patient [50]. AFP levels often decline slowly to reach normal levels in the very young, but a continued decline should be present [51].

SURGICAL RESECTION — In most cases, surgical resection is undertaken postnatally. In utero interventions are generally only temporizing measures, allowing the fetus to recover in utero and continue to grow and mature; in selected cases at specialized centers, resection may be undertaken in utero. (See 'Perinatal management' above.)

For tumors deemed resectable at diagnosis, maximal safe resection is recommended. Surgery for complete excision of an SCT often is quite extensive. It must include removal of the coccyx to be considered complete. Other considerations include early ligation of the sacral vessels and sterile circumferential preparation of the body due to the potential need for intraoperative change in approach [52]. If a complete resection cannot be achieved in the first surgery, a second procedure may be required to complete the resection, particularly for tumors with malignant elements [10,53].

Despite successful control of the tumor in the majority of patients, functional sequelae are common and can impair quality of life [54,55]. The frequency of serious complications was assessed in a series of 79 patients from the Netherlands who were treated from 1980 to 2003 [54]. Bowel dysfunction (soiling, including total fecal incontinence in some cases) was reported in 13 percent and urinary incontinence was observed in 31 percent. In a more recent series of 45 patients treated from 2000 to 2013 in the United States, anorectal complications occurred in 29 percent and urologic complications occurred in 33 percent [56]. No anorectal or urologic complications occurred in patients with Altman type I tumors.

POSTOPERATIVE THERAPY

Benign SCT — The majority of SCTs do not contain malignant elements. Early, complete surgical resection is the cornerstone of management for mature and immature SCTs in this setting [2,8,9,12,18,57,58]. Surgical resection is often an extensive procedure and can cause significant acute and long-term side effects. (See 'Surgical resection' above.)

Incomplete resections are associated with a significantly higher rate of recurrence. In a German series, recurrence was more frequent after incomplete resection (49 versus 11 percent, in those with complete resection) [12]. Similarly, the Children's Cancer Group (CCG) observed a recurrence rate of 11 percent in patients with mature SCT [4]. Of these, two recurrences were mature teratoma, while the remaining seven had yolk sac tumors [4].

Both German and United Kingdom investigators found no benefit for adjuvant chemotherapy in patients with immature teratoma [8,12]. Similarly, the American Intergroup study demonstrated that observation after complete resection was an effective strategy in patients with immature teratoma [9].

SCT with malignant elements — SCTs with malignant elements are staged postoperatively following Children's Oncology Group (COG) staging guidelines for extragonadal germ cell tumors (GCTs) (table 1). Stage I refers to completely resected tumors with negative pathologic margins and no evidence of lymph node involvement. Stage II includes resected tumors with microscopic residual disease but negative lymph nodes. Stage III includes patients with gross residual/unresectable tumor or positive lymph nodes, and stage IV refers to patients with distant metastases.

The natural history and prognosis of malignant SCTs vary by stage and inform the treatment approach. Stage I and II malignant SCTs treated with complete surgical resection and chemotherapy have an overall survival (OS) at five years that exceeds 90 percent [10,59,60]. Metastatic tumors have a lower event-free survival (EFS) and OS. In a combined analysis of three German trials that utilized surgery followed by a five-drug chemotherapy regimen, outcomes were worse for those with metastatic tumors (five-year EFS 67 versus 83 percent in those without metastases, and OS 69 versus 92 percent) [10].

●Stage I – For stage I SCTs with malignant elements, the treatment approach has evolved, and many pediatric oncologists prefer a watch-and-wait strategy rather than proceeding immediately with adjuvant chemotherapy. These patients are often infants, and a period of watch-and-wait postpones and sometimes avoids the toxicities of chemotherapy while the child has time to grow and mature.

Limited observation data suggest that this is a reasonable strategy. A case series and review of the literature identified 14 cases of stage I SCT with malignant components, 12 of whom survived with no recurrence at last follow-up, ranging from two to eight years [61]. Two patients who recurred were treated with platinum-based chemotherapy and were alive at nine years.

The shift towards observation for stage I SCTs with malignant elements is reflected in cooperative group trial design. In the actively enrolling COG trial (AGCT 1531), stage I extragonadal GCTs such as SCT are observed without immediate chemotherapy, whereas in the last completed trial (AGCT 0132), patients with a completely resected malignant SCT were considered to have intermediate-risk disease and received at least three cycles of BEP (bleomycin, etoposide, and cisplatin) therapy [62].

●Stage II – For stage II SCTs with malignant elements, adjuvant chemotherapy remains the standard of care, using a platinum-based multidrug regimen such as such as BEP or BEJ (bleomycin, etoposide, and carboplatin) [59,60,62].

●Stages III and IV – For patients with advanced disease, neoadjuvant chemotherapy has been used prior to an attempt at complete resection [12,53,59]. In patients with locally advanced or metastatic disease, those who received neoadjuvant chemotherapy followed by resection had an EFS of 79 percent with an OS of 83 percent at five years, while those who had an immediate attempt at complete resection had both EFS and OS of 49 percent [12]. The American Intergroup data showed similar results, with all nonthoracic, extragonadal GCTs having an EFS and OS of 82 and 87 percent, respectively, at five years [53]. In the United Kingdom Children's Cancer Study Group (UKCCSG) experience, patients with malignant sacrococcygeal GCT who were treated with neoadjuvant chemotherapy with BEJ had an EFS of 87 percent [59].

SURVEILLANCE AND RELAPSE — Children require regular follow-up after surgical resection or completion of chemotherapy. Surveillance guidance is based on expert opinion and clinical experience and typically involves clinical examination at three- to six-month intervals, with monthly tumor marker measurement (alpha-fetoprotein [AFP]) and lactate dehydrogenase (LDH) for the first year and then every two to six months. Primary site imaging (usually MRI) and chest radiograph are obtained at 3 and 12 months after resection and then as needed for evaluation of new symptoms. Follow-up should continue for at least three to five years, as late recurrences have been reported [4,63].

As discussed above (see 'Postnatal evaluation' above), interpretation of an elevated AFP after surgical resection can be difficult in infants and must consider the age of the patient [50]. AFP levels often decline slowly after birth and can take months to reach normal levels, but a continued decline should be present [50,51,64,65].

Approximately three-quarters of children with recurrent SCT will have an elevated AFP, including some who had mature teratoma initially [66]. Most recurrences are detected through physical examination or high AFP levels; others may be diagnosed by MRI, CT, or ultrasound after symptoms such as constipation are reported [63].

Both mature and immature teratomas can recur locally and at distant sites, and recurrence is associated with decreased overall survival (OS) [9,12]. The overall recurrence rate is approximately 10 percent for mature teratomas and approximately 20 percent for immature teratomas. The vast majority of patients with distant relapse also have recurrent locoregional disease [12]. In addition to immature or malignant histology, risk factors for recurrence include incomplete resection and tumor spillage at the time of surgery [67].

TREATMENT OF RECURRENCE — Patients with recurrent disease are treated with further surgery or chemotherapy depending upon the pathology and extent of the recurrent tumor. SCT patients who recur with malignant elements can often be salvaged with platinum-based therapy [8,9,12]. (See 'SCT with malignant elements' above.)

Patients previously treated with chemotherapy (cisplatin [BEP] or carboplatin [JEB]) for malignant disease can be treated with a number of salvage regimens for recurrent malignant germ cell tumor (GCT) including paclitaxel, ifosfamide, and cisplatin [68]; vinblastine, ifosfamide, and platinum [69]; and high-dose chemotherapy with stem cell rescue [55,70-72]. The most recent Children's Oncology Group (COG) study for refractory GCTs used a combination of paclitaxel, ifosfamide, and carboplatin [73]. The study showed a good response rate in typical, younger patients with SCT, but this combination did not appear superior to other regimens used in the adolescent and young adult population.

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Sacrococcygeal teratoma (SCT) is the most common germ cell tumor (GCT) in infancy and early childhood (figure 1). SCTs are generally benign tumors. However, malignant elements can be present, and their frequency increases with the postnatal age of the patient. (See 'Epidemiology' above.)

●Prenatal detection and monitoring – As most SCTs are identified during pregnancy, serial ultrasound evaluation of the fetus, placenta, and tumor over the course of the gestation is an important component in the overall treatment plan (picture 2). The major goal is to identify fetuses at increased risk of fetal demise because of hydrops (ie, abnormal fetal fluid collections), and intervene as appropriate. (See 'Evaluation and monitoring' above.)

●Perinatal management – In most cases, surgical resection is undertaken postnatally. In utero interventions are generally only temporizing measures, allowing the fetus to recover in utero and continue to grow and mature; in very selected cases at specialized centers, resection may be undertaken in utero. (See 'Perinatal management' above and 'Surgical resection' above.)

●Postnatal management

•Benign SCT – For benign (mature and immature) SCTs, early, complete surgical resection is the cornerstone of management. There does not appear to be a role for adjuvant chemotherapy following surgery. (See 'Benign SCT' above.)

•SCT with malignant elements, stage I or II – For tumors deemed resectable at diagnosis, maximal safe resection should be undertaken. Postoperatively, the approach depends on staging (table 1).

For most patients with stage I disease (complete resection, negative pathologic margins), we suggest observation rather than immediate chemotherapy (Grade 2C). For patients with stage II disease (microscopic residual, negative lymph nodes), adjuvant chemotherapy remains the standard of care. We suggest a platinum-based regimen such as cisplatin (BEP) or carboplatin (BEJ), rather than alternative chemotherapeutic regimens (Grade 2C). (See 'SCT with malignant elements' above.)

•SCT with malignant elements, locally advanced or metastatic – For patients with locally advanced or metastatic malignant SCTs, we suggest neoadjuvant platinum-based chemotherapy (prior to attempted surgical resection), rather than adjuvant chemotherapy (Grade 2C).

●Posttreatment surveillance – Children require regular clinical, laboratory, and imaging follow-up after surgical resection or completion of chemotherapy. Follow-up should continue for at least three to five years, as late recurrences have been reported. (See 'Surveillance and relapse' above.)