Diagnosis, management and outcome of teratomas in neonates and infants: A multi-institutional study
Purpose: Teratomas, the most common tumor affecting neonates, has an estimated incidence of 1 in 20,000 to 30,000 live births. The study was designed to determine the effect of therapy on the long-term outcome of neonates and infants with teratomas.Methods: A retrospective analysis was conducted of neonates and small infants with teratomas treated from 1972-1997 at 17 Childrens Hospitals in the United States.
Results: Teratomas, the most common neoplasm in neonates and young infants accounted for over 40% of all solid tumors observed in this age population. In this study, 158 children were diagnosed with teratomas. The sacrococcygeal location was predominant with 131 (84%). Sacrococcygeal teratomas (SCT) were prenatally diagnosed in 33, at birth in 82 and later in infancy in 16. There were 97 females and 34 males. At presentation, 70% of SCT were mature teratoma, 20% were immature teratoma and 10% had endodermal sinus tumor (EST). Mean follow-up was 7 years. Five percent of the infants died within the perioperative period. Nine patients (10%) who had mature SCT developed recurrent disease; 2 had locally recurring mature teratoma and 7 had EST. One child with an immature SCT had recurrent tumor at a local site. Seven of 13 EST infants were disease free after chemotherapy (CTX) and 6 had received no adjunctive CTX. Two of the 6 later developed evidence of metastatic disease within 1 year and were salvaged with CTX (bleomycin, etoposide, vinblastine, cisplatin). Cervicofacial teratomas were diagnosed in 21 (13%). Fifteen neonates had cervical teratomas and 6 infants presented with orofacial teratomas. There were 12 males and 9 females. A diagnostic prenatal ultrasound was performed in 8 cases. Life-threatening airway obstruction occurred in 8 infants (38%) in the early postnatal period. Three neonates died in the delivery room without ever having their airway secured. Two other prenatally diagnosed infants survived only because tracheostomies were performed by pediatric surgeons who were in the delivery room. Three others had oral intubation, one after sustaining a hypoxic cardiac arrest. Eighteen infants had their primary tumor excised. After resection 2 patients had evidence of unilateral recurrent laryngeal nerve injury, and 2 required thyroid hormone replacement. Histology revealed 8 mature and 7 immature teratomas. Four infants (18%) clearly had malignant lesions. Pulmonary metastases occurred in 2 children and contributed to one late death at 6 months. Overall survival was 77% with a mean follow-up of 6 years (range 2-16 years). Twelve of 17 (70%) surviving patients have had excellent functional and cosmetic outcomes. Four children have varying degrees of developmental delay and mental retardation. Hypoxia at birth was felt to have contributed to these problems in 2. Four retroperitoneal and 2 mediastinal tumors were diagnosed and all infants survived surgical therapy.
Keywords: TERATOMA-diagnosis, therapy, mortality; INFANT; NEWBORN
INFANT
INTRODUCTION
Teratomas are unusual tumors occurring with a reported incidence of one in 30,000 live births (1). Sacrococcygeal and cervicofacial teratomas represent the most common sites for extragonadal germ cell tumors in neonates and early childhood and account for more than 70% of teratomas in most series (2). The surgical committee of the Childrens Cancer Group conducted a multi-institutional study to correlate the effect of modern therapy with the long-term outcome of these patients with these unusual neoplasms.
METHODS
A retrospective analysis of 158 neonates and infants presenting with sacrococcygeal teratomas between 1972 and 1997 was performed. Seventeen Childrens Cancer Group (CCG) institutions participated in the review. Patient records were reviewed; and demographic information, diagnostic modalities, therapy, pathology and outcome data were abstracted onto questionnaires and collated. The clinical data and follow-up information were provided by each institutional surgeon.
RESULTS
Sacrococcygeal tumors
One hundred thirty-one children presented with sacrococcygeal tumors (Table 1) (Figure 1a, b). The lesions were identified prenatally by ultrasound scan in 33, at birth in 82, and later in infancy in 16. There were 97 girls and 34 boys. Chromosomal abnormalities included one child with trisomy 13 and another with trisomy 21. Six of the 16 who underwent diagnosis in infancy had a sacral mass noted at birth; in two instances the presumptive diagnosis was hemangioma, in one an anterior meningocele, and in the remainder the diagnosis was not specified. The diagnosis was confirmed between 1.5 and 34 months (average, 11 months) with one child presenting with metastatic tumor at 10 months of age. The remaining 10 who underwent diagnosis past the neonatal period presented from 2 to 30 months (average, 10.1 months). They included four with associated anal stenosis (three also with spinal dysraphism) and one noted at time of myelomeningocele repair. There was a positive family history in two sisters who presented at 11 and 26 months of age with rectal stenosis, sacral dysraphism, and sacrococcygeal teratomas (SCT). Associated defects included myelomeningocele/sacral dysraphism in four, imperforate anus in one, anal stenosis/anterior displacement in four, hydronephrosis in one, mitral insufficiency in, one and pulmonary hypoplasia in one.
A postnatal ultrasound scan was performed in 61 patients to evaluate the degree of pelvic and abdominal extension. Additional tests in 21 neonates and infants included intravenous pyelogram (n=12), cystogram (n=5), barium enema (n=10), arteriogram (n=2), bone scan (n=1), and tumor cyst injection (n=1). The arteriogram finding showed a hypervascular tumor in one and hypovascular tumor in the other. Alpha-feta-protein (AFP) levels were determined preoperatively in 53 patients. The AFP was elevated in 42 and normal in 11 with 5 of the normal levels occurring in older infants. Two neonates with SCT and severe associated defects died without surgical intervention. One had pulmonary hypoplasia and cardiac failure and the other Trisomy 21 with cloacal exstrophy, imperforate anus, and Arnold Chiari malformation with associated hydrocephalus.
Surgical management
Operative resection was performed in the remaining 129. Resection was performed via a sacral approach only in 101 and by a combination abdominosacral approach in 28. In two neonates, the abdominal portion was performed on the second day of life with the sacral portion delayed to day 5 and 11. One child had a temporary protective colostomy created at the initial procedure. The CCG/Pediatric Oncology Group (POG) staging system was used. There were 126 stage I lesions, two stage II with microscopic residual, and one stage IV with metastases to inguinal lymph nodes. Seven neonates (5.5%) died within 30 days of surgery. Hemorrhagic shock related to tumor resection developed in two full-term infants with large tumors. Coagulopathy and continued bleeding led to cardiac arrest and death within 48 hours of surgery. The other five patients had severe associated factors present preoperatively including prematurity in four (average, 30 weeks), failed attempt at vaginal delivery with subsequent emergency caesarean section and resultant birth asphyxia in two, and preoperative rupture in one. The remaining 123 patients were available for long-term follow-up. Pathology and longterm followup
Histological examination showed 93 mature teratomas, 25 immature teratomas, and 13 endodermal sinus tumors (EST).
Mature teratoma. Recurrent disease developed in nine of 89 patients (10%) with mature teratoma between six and 34 months after the initial resection (Table 2). Two of the recurrences were mature teratomas that were noted on rectal examination 6 months post-resection and treated with surgery alone. Both patients with recurrence are long-term survivors. Seven of the recurrences were found to be ESTs and presented as a gluteal mass in two patients, hepatomegaly in two, inguinal lymphadenopathy in one, a rising AFP level in one, and was not specified in one patient. Three had metastatic disease. Treatment in two patients presenting before 1979 was surgery plus vincristine, dactinomycin, and cyclophosphamide (VAC) with one receiving pelvic radiation. Two recurrences occurring in the early 1980s were treated on CCG 861 with vinblastine, bleomycin, cisplatin, cyclophosphamide, dactinomycin, and doxorubicin. Three recurrences detected in the late 1980s and early 1990s were treated with cisplatin, etoposide, and bleomycin (PEB). Six of seven (85.7%) are alive with mean follow-up of 114 months, and one with metastatic disease was lost to follow-up.
Immature teratoma. Twenty-five children with immature teratoma were followed-up for an average of 39 months. One child was noted to have a rising AFP level 6 months after the initial procedure and underwent resection of a mature teratoma. The child is free of disease 33 months after the second procedure.
Endodermal sinus tumor. Thirteen neonates and infants underwent initial surgery with findings of EST. In ten patients the lesion was noted at birth, and nine underwent early surgery with complete resection. Seven of these are long-term survivors, whereas two died of non-disease-related causes: one with Trisomy 13, and one child born prematurely died of respiratory and renal failure. The two non-disease related deaths were eliminated from analysis. One child with the lesion observed after birth presented with metastatic disease at 10 months of age and underwent incomplete resection of the primary tumor at that time. She died despite adjuvant therapy. Three other patients presented between 7 and 30 months of age without evidence of metastatic disease, underwent complete resection, and are long-term survivors. Six children with EST received no chemotherapy. Recurrent disease developed in two of the six (33%); one had a suture line recurrence at 3 months and one had local and metastatic recurrence at 11 months. Both were treated on CCG 861 with vinblastine, bleomycin, cisplatin, cyclophosphamide, dactinomycin, and doxorubicin and are disease free 113 and 116 months after recurrence, respectively. The remaining five EST children received initial chemotherapy. Four with non-metastatic tumors are free of recurrence and are alive at long-term follow-up (60 months). The other child presented at 10 months of age with a metastatic lesion after the sacral lesion was observed since birth. Despite chemotherapy with PEB, VAC, and doxorubicin, the child died at 34 months of age. Of all the 18 EST children (11 presentation, 7 recurrent teratoma) followed-up after resection, 16 (89%) are free of disease with a mean follow-up of 91 months.
Cervicofacial teratomas. Fifteen neonates presented with cervical teratomas and 6 with orofacial lesions (Figure 2a, b). There were 12 males and 9 females. Ultrasound studies performed during the late second or early third trimester yielded a prenatal diagnosis in 7 pregnancies. Polyhydramnios was the indication for maternal-fetal ultrasonography in 4 cases. The remaining 14 infants were diagnosed at birth or in the early postnatal period. Significant craniofacial and/or central nervous system anomalies were documented in 4 infants. One infant with a cervical teratoma had craniosynostosis. Two neonates with orofacial teratomas had hydrocephalus and one had a cleft palate. Three of the infants were born prematurely (30-35 weeks).
Significant airway compromise was documented in 8 infants (38%). Life-threatening airway obstruction occurred in the delivery room in 7 infants and 72 hours after birth in another. Three children died in the delivery room without ever having their airway secured. Two prenatally diagnosed infants survived only because tracheostomies were performed after multiple unsuccessful attempts at orotracheal intubation (Figure 2a, b). In one patient who required tracheostomy, endoscopic visualization of the airway was attempted but the larynx could not be seen due to severe anatomic distortion. The presence of a pediatric surgeon in the delivery room was cruical for successful airway management in both these patients. Orotracheal intubation was accomplished in 3 other infants, one of whom was successfully resuscitated following a hypoxic cardiac arrest.
Of the 18 surviving infants, 16 underwent gross total excision of the primary tumor in one operation (Figure 3a, b). One child with a large orofacial teratoma required 2 procedures before the surgical margins were free of tumor. Another infant with a large orofacial teratocarcinoma required 3 operations and intraoperative radiation before local tumor control was achieved. Some portion of the thyroid gland was excised in 6 patients and 2 children have required prolonged thyroid hormone replacement. Following resection of a cervical teratoma, one of these children also had a unilateral marginal mandibular nerve injury and hypoparathyroidism which resolved after one year. Unilateral vocal cord paralysis was observed in 2 infants presumably as a result of recurrent laryngeal nerve injuries. Minor tracheostomy complications occurred in all 3 patients who required tracheostomies but all were decannulated successfully. Serum alpha fetoprotein levels (AFP) was measured in 4 infants and the only patient with markedly elevated levels had a teratocarcinoma.
Histologic analysis revealed 8 mature and 7 immature teratomas. Two infants who died in the delivery room did not have a post mortem examination. Four infants (20%) had clearly malignant lesions. A fifth infant who was felt to have malignant teratoma at the time of initial treatment, in retrospect probably had a benign cervical teratoma with immature neural tissue but no evidence of metastases. There were 2 cervical and 2 orofacial malignant teratomas. Both malignant cervical teratomas had evidence of metastases at birth. One child with foci of neuroblastoma in an immature teratoma had both pleural and pulmonary metastases. This infant succumbed at 6 months of age from disseminated neuroblastoma. The second child had neuroblastoma-like cells and neural stromal cells in the primary tumor and metastases in the liver, lung and the subcutaneous tissue of the buttock. This infant was successfully treated with sequential resection of the teratoma, hepatic trisegmentectomy, left lower lobectomy and excision of the buttock soft tissue mass. The histology of the excised metastases was similar to the primary tumor but appeared significantly more differentiated. This patient remains alive without evidence of recurrent disease at 7 years of age. Of the 2 malignant orofacial teratomas, one was a teratocarcinoma of the cheek and mandible with intracranial extension. After an incisional biopsy establishing the diagnosis, the patient required two additional operations including a partial craniectomy with intraoperative radiation (1000 cGy) to the mandible. This patient was also treated with Vincristine, Actinomycin-D, Cytoxan, Vinblastine, Bleomycin, Cisplatinum, and Adriamycin for 24 months and she remains disease free at 9 years of age. The other infant who had an invasive orbital and facial teratoma underwent gross total excision with enucleation of the orbit, chemotherapy with Vincristine, Actinomycin-D and Cytoxan as well as 3,400 cGy to the face and head. This patient remains alive without disease 12 years later. One infant succumbed with disseminated neuroblastoma at 6 months of age. Seventeen children (85%) survived longer than one year with mean follow-up of 5 years (range 2 months to 16 years). Twelve of seventeen (70%) surviving patients have had an excellent cosmetic and functional outcome. One child has a mild congenital hearing deficit. All three infants with tracheostomies have been successfully decannulated. Four children have varying degrees of developmental delay and mental retardation. Airway obstruction and hypoxia at birth were felt to have produced these problems in 2 infants (one of whom had 2 operations for craniosynostosis). A third infant with developmental delay and severe mental retardation received 3,400 cGy of cranial irradiation as a neonate. The patient also has orbit and malar hypoplasia. A fourth child with mild developmental delay had congenital hydrocephalus. Severe left hemifacial hypoplasia and facial asymmetry occurred in another child with an invasive teratocarcinoma who had received radiation (1,000 cGy) to the mandible. After receiving intensive multi-agent chemotherapy, this young girl developed renal failure and required temporary peritoneal dialysis. She has subsequently undergone 3 reconstructive surgical procedures and remains free of disease with otherwise normal development at age 9 years.
Mediastinal and retroperitoneal teratomas
Four infants had retroperitoneal teratomas and two had mediastinal tumors diagnosed. All infants were rendered disease free by treatment and all were long-term survivors. Two of the retroperitoneal tumors were mature teratomas, one had immature elements by histology. One was malignant with evidence of regional node metastases. All patients had surgical resections. The patient with the malignant teratoma had multiagent chemotherapy in addition to surgical resection and was disease free at 2 year follow-up. The retroperitoneal teratomas were both immature. One was removed from the posterior mediastinum of a 4 months old infant who presented with severe respiratory distress. The other was an intracardiac teratoma successfully resected from a neonate. Follow-up averaged 7 years for these 2 infants.
DISCUSSION
Most tumors at the sacrococcygeal region are mature or immature teratomas and less commonly endodermal sinus tumors. Children with malignant extragonadal tumors have generally had a worse prognosis than gonadal tumors, although this difference may be less apparent with the advent of cisplatin-based chemotherapy (3).
As in prior reports, this study shows a female predominance with a 3 to 4:1 ratio (4, 5). Patients with sacrococcygeal tumors generally present in two clinical patterns; the most common involves those presenting in the neonatal period with large predominantly benign tumors that are usually mature or immature teratomas, and the less common pattern involves infants and children presenting between birth and 4 years of age with lesions primarily in the pelvis and predominantly malignant. Newborns generally have the characteristic mass protruding from the sacral region. The lesion is frequently diagnosed by prenatal ultrasound scan and infants with tumors greater than 5 cm in size should be considered for abdominal delivery to avoid dystocia and tumor rupture (6). Other fetal problems include polyhydramnios, preterm delivery with lung immaturity and tumor hemorrhage with anemia and hydrops. Hydrops can also occur from high output cardiac failure if the tumor behaves as an arteriovenous fistula (7). Flake et al (6), in a collective review of fetal sacrococcygeal teratomas noted that most present between 22 and 34 weeks with an enlarged uterus or polyhydramnios. They noted improved survival with later presentation, with 75% of fetuses diagnosed after 30 weeks gestation surviving compared with only 7% of those presenting before 30 weeks gestation. The development of hydrops is an ominous sign and if diagnosed after 30 weeks gestation, delivery should occur as soon as the lungs are mature. Fetuses less than 30 weeks gestation with hydrops may benefit from in utero surgery. Two fetal SCT resections have been reported; however, delivery occurred prematurely in each case, and both died (8).
Although most neonatal cases are apparent at delivery, some are small with minimal external deformity and some are entirely within the pelvis. Altman et al (5), in the survey of the Surgical Section of the American Academy of Pediatrics (AAP) classified tumors according to the degree of pelvic extension: type 1 (46.7%), predominantly external; type 11 (34.7%), external with significant intrapelvic extension; type 111 (8.8%), visible externally but predominantly pelvic and abdominal extension; and type IV (9.8%), entirely presacral. The occurrence of malignancy appears related to age at presentation and age at resection. In the AAP survey (5), the rate of malignancy increased with less apparent lesions (type II to IV) as well with older age at diagnosis (under 2 months, 7% girls and 10% boys malignant; over 2 months, 48% girls and 67% boys malignant). Donnellan and Swenson (12) noted that after 2 months of age, 91.7% were malignant. Malignancy rates in the 50% to 90% range have been noted by others as well as in older infants (10, 11). Altman et al (5), suggested that the higher malignancy rate in older infant was caused by a delay in diagnosis of the less apparent lesions. In the present study, a delay in diagnosis in six neonates resulted in a 33% malignancy rate and accounted for the only known disease-related death in this series. In the present study, of the 111 neonates with the diagnosis of histologically confirmed SCT, 10 (9%) were malignant compared with 4 of 15 (27%) malignancies in the older group (12).
INTRODUCTION
Teratomas are unusual tumors occurring with a reported incidence of one in 30,000 live births (1). Sacrococcygeal and cervicofacial teratomas represent the most common sites for extragonadal germ cell tumors in neonates and early childhood and account for more than 70% of teratomas in most series (2). The surgical committee of the Childrens Cancer Group conducted a multi-institutional study to correlate the effect of modern therapy with the long-term outcome of these patients with these unusual neoplasms.
METHODS
A retrospective analysis of 158 neonates and infants presenting with sacrococcygeal teratomas between 1972 and 1997 was performed. Seventeen Childrens Cancer Group (CCG) institutions participated in the review. Patient records were reviewed; and demographic information, diagnostic modalities, therapy, pathology and outcome data were abstracted onto questionnaires and collated. The clinical data and follow-up information were provided by each institutional surgeon.
RESULTS
Sacrococcygeal tumors
One hundred thirty-one children presented with sacrococcygeal tumors (Table 1) (Figure 1a, b). The lesions were identified prenatally by ultrasound scan in 33, at birth in 82, and later in infancy in 16. There were 97 girls and 34 boys. Chromosomal abnormalities included one child with trisomy 13 and another with trisomy 21. Six of the 16 who underwent diagnosis in infancy had a sacral mass noted at birth; in two instances the presumptive diagnosis was hemangioma, in one an anterior meningocele, and in the remainder the diagnosis was not specified. The diagnosis was confirmed between 1.5 and 34 months (average, 11 months) with one child presenting with metastatic tumor at 10 months of age. The remaining 10 who underwent diagnosis past the neonatal period presented from 2 to 30 months (average, 10.1 months). They included four with associated anal stenosis (three also with spinal dysraphism) and one noted at time of myelomeningocele repair. There was a positive family history in two sisters who presented at 11 and 26 months of age with rectal stenosis, sacral dysraphism, and sacrococcygeal teratomas (SCT). Associated defects included myelomeningocele/sacral dysraphism in four, imperforate anus in one, anal stenosis/anterior displacement in four, hydronephrosis in one, mitral insufficiency in, one and pulmonary hypoplasia in one.
A postnatal ultrasound scan was performed in 61 patients to evaluate the degree of pelvic and abdominal extension. Additional tests in 21 neonates and infants included intravenous pyelogram (n=12), cystogram (n=5), barium enema (n=10), arteriogram (n=2), bone scan (n=1), and tumor cyst injection (n=1). The arteriogram finding showed a hypervascular tumor in one and hypovascular tumor in the other. Alpha-feta-protein (AFP) levels were determined preoperatively in 53 patients. The AFP was elevated in 42 and normal in 11 with 5 of the normal levels occurring in older infants. Two neonates with SCT and severe associated defects died without surgical intervention. One had pulmonary hypoplasia and cardiac failure and the other Trisomy 21 with cloacal exstrophy, imperforate anus, and Arnold Chiari malformation with associated hydrocephalus.
Surgical management
Operative resection was performed in the remaining 129. Resection was performed via a sacral approach only in 101 and by a combination abdominosacral approach in 28. In two neonates, the abdominal portion was performed on the second day of life with the sacral portion delayed to day 5 and 11. One child had a temporary protective colostomy created at the initial procedure. The CCG/Pediatric Oncology Group (POG) staging system was used. There were 126 stage I lesions, two stage II with microscopic residual, and one stage IV with metastases to inguinal lymph nodes. Seven neonates (5.5%) died within 30 days of surgery. Hemorrhagic shock related to tumor resection developed in two full-term infants with large tumors. Coagulopathy and continued bleeding led to cardiac arrest and death within 48 hours of surgery. The other five patients had severe associated factors present preoperatively including prematurity in four (average, 30 weeks), failed attempt at vaginal delivery with subsequent emergency caesarean section and resultant birth asphyxia in two, and preoperative rupture in one. The remaining 123 patients were available for long-term follow-up. Pathology and longterm followup
Histological examination showed 93 mature teratomas, 25 immature teratomas, and 13 endodermal sinus tumors (EST).
Mature teratoma. Recurrent disease developed in nine of 89 patients (10%) with mature teratoma between six and 34 months after the initial resection (Table 2). Two of the recurrences were mature teratomas that were noted on rectal examination 6 months post-resection and treated with surgery alone. Both patients with recurrence are long-term survivors. Seven of the recurrences were found to be ESTs and presented as a gluteal mass in two patients, hepatomegaly in two, inguinal lymphadenopathy in one, a rising AFP level in one, and was not specified in one patient. Three had metastatic disease. Treatment in two patients presenting before 1979 was surgery plus vincristine, dactinomycin, and cyclophosphamide (VAC) with one receiving pelvic radiation. Two recurrences occurring in the early 1980s were treated on CCG 861 with vinblastine, bleomycin, cisplatin, cyclophosphamide, dactinomycin, and doxorubicin. Three recurrences detected in the late 1980s and early 1990s were treated with cisplatin, etoposide, and bleomycin (PEB). Six of seven (85.7%) are alive with mean follow-up of 114 months, and one with metastatic disease was lost to follow-up.
Immature teratoma. Twenty-five children with immature teratoma were followed-up for an average of 39 months. One child was noted to have a rising AFP level 6 months after the initial procedure and underwent resection of a mature teratoma. The child is free of disease 33 months after the second procedure.
Endodermal sinus tumor. Thirteen neonates and infants underwent initial surgery with findings of EST. In ten patients the lesion was noted at birth, and nine underwent early surgery with complete resection. Seven of these are long-term survivors, whereas two died of non-disease-related causes: one with Trisomy 13, and one child born prematurely died of respiratory and renal failure. The two non-disease related deaths were eliminated from analysis. One child with the lesion observed after birth presented with metastatic disease at 10 months of age and underwent incomplete resection of the primary tumor at that time. She died despite adjuvant therapy. Three other patients presented between 7 and 30 months of age without evidence of metastatic disease, underwent complete resection, and are long-term survivors. Six children with EST received no chemotherapy. Recurrent disease developed in two of the six (33%); one had a suture line recurrence at 3 months and one had local and metastatic recurrence at 11 months. Both were treated on CCG 861 with vinblastine, bleomycin, cisplatin, cyclophosphamide, dactinomycin, and doxorubicin and are disease free 113 and 116 months after recurrence, respectively. The remaining five EST children received initial chemotherapy. Four with non-metastatic tumors are free of recurrence and are alive at long-term follow-up (60 months). The other child presented at 10 months of age with a metastatic lesion after the sacral lesion was observed since birth. Despite chemotherapy with PEB, VAC, and doxorubicin, the child died at 34 months of age. Of all the 18 EST children (11 presentation, 7 recurrent teratoma) followed-up after resection, 16 (89%) are free of disease with a mean follow-up of 91 months.
Cervicofacial teratomas. Fifteen neonates presented with cervical teratomas and 6 with orofacial lesions (Figure 2a, b). There were 12 males and 9 females. Ultrasound studies performed during the late second or early third trimester yielded a prenatal diagnosis in 7 pregnancies. Polyhydramnios was the indication for maternal-fetal ultrasonography in 4 cases. The remaining 14 infants were diagnosed at birth or in the early postnatal period. Significant craniofacial and/or central nervous system anomalies were documented in 4 infants. One infant with a cervical teratoma had craniosynostosis. Two neonates with orofacial teratomas had hydrocephalus and one had a cleft palate. Three of the infants were born prematurely (30-35 weeks).
Significant airway compromise was documented in 8 infants (38%). Life-threatening airway obstruction occurred in the delivery room in 7 infants and 72 hours after birth in another. Three children died in the delivery room without ever having their airway secured. Two prenatally diagnosed infants survived only because tracheostomies were performed after multiple unsuccessful attempts at orotracheal intubation (Figure 2a, b). In one patient who required tracheostomy, endoscopic visualization of the airway was attempted but the larynx could not be seen due to severe anatomic distortion. The presence of a pediatric surgeon in the delivery room was cruical for successful airway management in both these patients. Orotracheal intubation was accomplished in 3 other infants, one of whom was successfully resuscitated following a hypoxic cardiac arrest.
Of the 18 surviving infants, 16 underwent gross total excision of the primary tumor in one operation (Figure 3a, b). One child with a large orofacial teratoma required 2 procedures before the surgical margins were free of tumor. Another infant with a large orofacial teratocarcinoma required 3 operations and intraoperative radiation before local tumor control was achieved. Some portion of the thyroid gland was excised in 6 patients and 2 children have required prolonged thyroid hormone replacement. Following resection of a cervical teratoma, one of these children also had a unilateral marginal mandibular nerve injury and hypoparathyroidism which resolved after one year. Unilateral vocal cord paralysis was observed in 2 infants presumably as a result of recurrent laryngeal nerve injuries. Minor tracheostomy complications occurred in all 3 patients who required tracheostomies but all were decannulated successfully. Serum alpha fetoprotein levels (AFP) was measured in 4 infants and the only patient with markedly elevated levels had a teratocarcinoma.
Histologic analysis revealed 8 mature and 7 immature teratomas. Two infants who died in the delivery room did not have a post mortem examination. Four infants (20%) had clearly malignant lesions. A fifth infant who was felt to have malignant teratoma at the time of initial treatment, in retrospect probably had a benign cervical teratoma with immature neural tissue but no evidence of metastases. There were 2 cervical and 2 orofacial malignant teratomas. Both malignant cervical teratomas had evidence of metastases at birth. One child with foci of neuroblastoma in an immature teratoma had both pleural and pulmonary metastases. This infant succumbed at 6 months of age from disseminated neuroblastoma. The second child had neuroblastoma-like cells and neural stromal cells in the primary tumor and metastases in the liver, lung and the subcutaneous tissue of the buttock. This infant was successfully treated with sequential resection of the teratoma, hepatic trisegmentectomy, left lower lobectomy and excision of the buttock soft tissue mass. The histology of the excised metastases was similar to the primary tumor but appeared significantly more differentiated. This patient remains alive without evidence of recurrent disease at 7 years of age. Of the 2 malignant orofacial teratomas, one was a teratocarcinoma of the cheek and mandible with intracranial extension. After an incisional biopsy establishing the diagnosis, the patient required two additional operations including a partial craniectomy with intraoperative radiation (1000 cGy) to the mandible. This patient was also treated with Vincristine, Actinomycin-D, Cytoxan, Vinblastine, Bleomycin, Cisplatinum, and Adriamycin for 24 months and she remains disease free at 9 years of age. The other infant who had an invasive orbital and facial teratoma underwent gross total excision with enucleation of the orbit, chemotherapy with Vincristine, Actinomycin-D and Cytoxan as well as 3,400 cGy to the face and head. This patient remains alive without disease 12 years later. One infant succumbed with disseminated neuroblastoma at 6 months of age. Seventeen children (85%) survived longer than one year with mean follow-up of 5 years (range 2 months to 16 years). Twelve of seventeen (70%) surviving patients have had an excellent cosmetic and functional outcome. One child has a mild congenital hearing deficit. All three infants with tracheostomies have been successfully decannulated. Four children have varying degrees of developmental delay and mental retardation. Airway obstruction and hypoxia at birth were felt to have produced these problems in 2 infants (one of whom had 2 operations for craniosynostosis). A third infant with developmental delay and severe mental retardation received 3,400 cGy of cranial irradiation as a neonate. The patient also has orbit and malar hypoplasia. A fourth child with mild developmental delay had congenital hydrocephalus. Severe left hemifacial hypoplasia and facial asymmetry occurred in another child with an invasive teratocarcinoma who had received radiation (1,000 cGy) to the mandible. After receiving intensive multi-agent chemotherapy, this young girl developed renal failure and required temporary peritoneal dialysis. She has subsequently undergone 3 reconstructive surgical procedures and remains free of disease with otherwise normal development at age 9 years.
Mediastinal and retroperitoneal teratomas
Four infants had retroperitoneal teratomas and two had mediastinal tumors diagnosed. All infants were rendered disease free by treatment and all were long-term survivors. Two of the retroperitoneal tumors were mature teratomas, one had immature elements by histology. One was malignant with evidence of regional node metastases. All patients had surgical resections. The patient with the malignant teratoma had multiagent chemotherapy in addition to surgical resection and was disease free at 2 year follow-up. The retroperitoneal teratomas were both immature. One was removed from the posterior mediastinum of a 4 months old infant who presented with severe respiratory distress. The other was an intracardiac teratoma successfully resected from a neonate. Follow-up averaged 7 years for these 2 infants.
DISCUSSION
Most tumors at the sacrococcygeal region are mature or immature teratomas and less commonly endodermal sinus tumors. Children with malignant extragonadal tumors have generally had a worse prognosis than gonadal tumors, although this difference may be less apparent with the advent of cisplatin-based chemotherapy (3).
As in prior reports, this study shows a female predominance with a 3 to 4:1 ratio (4, 5). Patients with sacrococcygeal tumors generally present in two clinical patterns; the most common involves those presenting in the neonatal period with large predominantly benign tumors that are usually mature or immature teratomas, and the less common pattern involves infants and children presenting between birth and 4 years of age with lesions primarily in the pelvis and predominantly malignant. Newborns generally have the characteristic mass protruding from the sacral region. The lesion is frequently diagnosed by prenatal ultrasound scan and infants with tumors greater than 5 cm in size should be considered for abdominal delivery to avoid dystocia and tumor rupture (6). Other fetal problems include polyhydramnios, preterm delivery with lung immaturity and tumor hemorrhage with anemia and hydrops. Hydrops can also occur from high output cardiac failure if the tumor behaves as an arteriovenous fistula (7). Flake et al (6), in a collective review of fetal sacrococcygeal teratomas noted that most present between 22 and 34 weeks with an enlarged uterus or polyhydramnios. They noted improved survival with later presentation, with 75% of fetuses diagnosed after 30 weeks gestation surviving compared with only 7% of those presenting before 30 weeks gestation. The development of hydrops is an ominous sign and if diagnosed after 30 weeks gestation, delivery should occur as soon as the lungs are mature. Fetuses less than 30 weeks gestation with hydrops may benefit from in utero surgery. Two fetal SCT resections have been reported; however, delivery occurred prematurely in each case, and both died (8).
Although most neonatal cases are apparent at delivery, some are small with minimal external deformity and some are entirely within the pelvis. Altman et al (5), in the survey of the Surgical Section of the American Academy of Pediatrics (AAP) classified tumors according to the degree of pelvic extension: type 1 (46.7%), predominantly external; type 11 (34.7%), external with significant intrapelvic extension; type 111 (8.8%), visible externally but predominantly pelvic and abdominal extension; and type IV (9.8%), entirely presacral. The occurrence of malignancy appears related to age at presentation and age at resection. In the AAP survey (5), the rate of malignancy increased with less apparent lesions (type II to IV) as well with older age at diagnosis (under 2 months, 7% girls and 10% boys malignant; over 2 months, 48% girls and 67% boys malignant). Donnellan and Swenson (12) noted that after 2 months of age, 91.7% were malignant. Malignancy rates in the 50% to 90% range have been noted by others as well as in older infants (10, 11). Altman et al (5), suggested that the higher malignancy rate in older infant was caused by a delay in diagnosis of the less apparent lesions. In the present study, a delay in diagnosis in six neonates resulted in a 33% malignancy rate and accounted for the only known disease-related death in this series. In the present study, of the 111 neonates with the diagnosis of histologically confirmed SCT, 10 (9%) were malignant compared with 4 of 15 (27%) malignancies in the older group (12).
Category: Original scientific paper
Volume: Vol. 43, No 4, october - december 1999
Authors: R. G. Azizkhan, F. J. Rescorla, G. M. Haase, H. Applebaum, P. W. Dillon, A. G. Coran, R. S. Sawin,P. A. King, D. R. King, D. S. Hodge
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