5
Neonatal teratomas Kokila Lakhoo Children's Hospital Oxford, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford OX3 9DU, United Kingdom abstract article info Keywords: Neonatal teratoma Teratomas are composed of multiple tissues foreign to the organ or site in which they arise. Their origin is postulated by 3 theories one of which is the origin from totipotent primodial germ cells. Anatomically, teratomas are divided into gonadal or extragonadal lesions and histologically they are classied as mature or immature tumors. Teratomas are mainy isolated lesions and may occur anywhere in the body. In the neonatal age group most of these tumors are benign and occur mainly in the sacrococcygeal area followed by the anterior mediastinum. Diagnosis is usually established prenatally and may require intervention in compromised fetuses. Postnatal imaging with ultrasound, CT scan or MRI provides useful information for surgical intervention. Complete surgical excision is the treatment of choice for neonatal teratomas. Alpha feto protein is the tumor marker of choice and is particularly useful for assessing the presence of residual or recurrent disease. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The term teratoma,is derived from the Greek word teratonmeaning a monster. Virchow in 1869 applied this term to a tumor originating in the sacrococcygeal region[1]. Teratomas are composed of multiple tissues foreign to the organ or site in which they arise. Most of the lesions present in neonatal period, and may be benign or malignant, and cystic or solid. Although teratomas are sometimes dened as having the three embryonic layers (endoderm, mesoderm, and ectoderm), recent classications include monodermal types [2]. The tumors can generally occur anywhere in the body, along the midline. This review focuses on neonatal teratomas,the most common being sacrococcygeal teratoma. 2. Aetiology Three theories are postulated.The rst theory supports the origin from the totipotent primordial germ cells [2]. These cells develop among the endodermal cells of the yolk sac near the origin of the allantois and migrate to the gonadal ridges during weeks 4 and 5 of gestation.Some cells may miss their target destination and give rise to a teratoma anywhere from the brain to the coccygeal area, usually in the midline.The second theory has teratomas arising from remnants of the primitive node [3]. During week 3 of development, midline cells at the caudal end of the embryo divide rapidly giving rise to all three germ layers of the embryo.By the end of week 3, the primitive streak shortens and disappears. This theory would explain the more common occurrence of teratomas in the sacrococcygeal region. The third theory has teratomas as an incomplete twinning [2]. 3. Classication Anatomically teratomas are divided into gonadal (testis or ovary) or extragonadal lesions.Histologically teratomas are classied as mature or immature on the basis of the presence of the immature neuroectoder- mal elements within the tumor. Mature teratoma comprises only mature elements such as the skin, hair, fat tissue, cartilage, bone, glands, etc. Immature teratoma contains immature elements such as neuroe- pithelial tissue and immature mesenchyme. The presence of micro- scopic foci of yolk sac tumor, rather than the histological grade of immaturity, is a valid predictor of recurrence. The grading of immature teratoma is unnecessary in neonates as the management is not altered and the prognosis is not altered [4]. Teratomas may also contain or develop foci of malignancy, and a malignant germ cell tumor may be found in sites typical for teratomas, such as the mediastinum or sacrococcygeal area. Whether the lesion was malignant from the onset or the malignant cells destroyed and replaced the benign teratoma component is often difcult to differen- tiate. The most common malignant component within a teratoma is a yolk sac tumor. Malignancy at birth is uncommon but increases with age and with incomplete resection. An apparently mature teratoma may recur several months or years after resection as a malignant yolk sac tumor, illustrating the difculties in histologic sampling of large tumors and the need for close follow-up [5]. Early Human Development 86 (2010) 643647 Tel.: +44 1865 234197; fax: +44 1865 234211. E-mail address: [email protected]. 0378-3782/$ see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2010.08.016 Contents lists available at ScienceDirect Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev

Neonatal Teratomas

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Page 1: Neonatal Teratomas

Early Human Development 86 (2010) 643–647

Contents lists available at ScienceDirect

Early Human Development

j ourna l homepage: www.e lsev ie r.com/ locate /ear lhumdev

Neonatal teratomas

Kokila Lakhoo ⁎Children's Hospital Oxford, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford OX3 9DU, United Kingdom

⁎ Tel.: +44 1865 234197; fax: +44 1865 234211.E-mail address: [email protected].

0378-3782/$ – see front matter © 2010 Elsevier Irelanddoi:10.1016/j.earlhumdev.2010.08.016

a b s t r a c t

a r t i c l e i n f o

Keywords:

Neonatal teratoma

Teratomas are composed of multiple tissues foreign to the organ or site in which they arise. Their origin ispostulated by 3 theories one of which is the origin from totipotent primodial germ cells. Anatomically,teratomas are divided into gonadal or extragonadal lesions and histologically they are classified as mature orimmature tumors. Teratomas are mainy isolated lesions and may occur anywhere in the body. In the neonatalage group most of these tumors are benign and occur mainly in the sacrococcygeal area followed by theanterior mediastinum. Diagnosis is usually established prenatally and may require intervention incompromised fetuses. Postnatal imaging with ultrasound, CT scan or MRI provides useful information forsurgical intervention. Complete surgical excision is the treatment of choice for neonatal teratomas. Alpha fetoprotein is the tumor marker of choice and is particularly useful for assessing the presence of residual orrecurrent disease.

Ltd. All rights reserved.

© 2010 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

The term “teratoma,” is derived from the Greek word “teraton”meaning “a monster”. Virchow in 1869 applied this term to a tumororiginating in the sacrococcygeal region[1]. Teratomas are composed ofmultiple tissues foreign to the organ or site in which they arise. Most ofthe lesions present in neonatal period, andmay be benign ormalignant,and cystic or solid. Although teratomas are sometimes defined ashavingthe three embryonic layers (endoderm, mesoderm, and ectoderm),recent classifications include monodermal types [2]. The tumors cangenerally occur anywhere in the body, along the midline. This reviewfocuses on neonatal teratomas,the most common being sacrococcygealteratoma.

2. Aetiology

Three theories are postulated.The first theory supports the origin fromthe totipotent primordial germ cells [2]. These cells develop among theendodermal cells of the yolk sac near the origin of the allantois andmigrate to thegonadal ridgesduringweeks4and5of gestation.Somecellsmay miss their target destination and give rise to a teratoma anywherefrom the brain to the coccygeal area, usually in the midline.The secondtheory has teratomas arising from remnants of the primitive node [3].During week 3 of development, midline cells at the caudal end of theembryodivide rapidly giving rise to all three germ layers of the embryo.By

the end of week 3, the primitive streak shortens and disappears. Thistheory would explain the more common occurrence of teratomas in thesacrococcygeal region. The third theory has teratomas as an incompletetwinning [2].

3. Classification

Anatomically teratomas are divided into gonadal (testis or ovary) orextragonadal lesions.Histologically teratomas are classified asmature orimmature on the basis of the presence of the immature neuroectoder-mal elements within the tumor. Mature teratoma comprises onlymature elements such as the skin, hair, fat tissue, cartilage, bone, glands,etc. Immature teratoma contains immature elements such as neuroe-pithelial tissue and immature mesenchyme. The presence of micro-scopic foci of yolk sac tumor, rather than the histological grade ofimmaturity, is a valid predictor of recurrence. The grading of immatureteratoma is unnecessary in neonates as the management is not alteredand the prognosis is not altered [4].

Teratomas may also contain or develop foci of malignancy, and amalignant germ cell tumor may be found in sites typical for teratomas,such as the mediastinum or sacrococcygeal area. Whether the lesionwas malignant from the onset or the malignant cells destroyed andreplaced the benign teratoma component is often difficult to differen-tiate. The most common malignant component within a teratoma is ayolk sac tumor.Malignancy at birth is uncommonbut increaseswith ageand with incomplete resection. An apparently mature teratoma mayrecur several months or years after resection as a malignant yolk sactumor, illustrating the difficulties in histologic sampling of large tumorsand the need for close follow-up [5].

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644 K. Lakhoo / Early Human Development 86 (2010) 643–647

3.1. Tumor markers

The tumor markers are common to all locations and the mostcommonly used one being Alpha-fetoprotein (AFP). This tumor markeris secreted by most yolk sac tumors and some embryonal carcinomasand can be measured in the serum and noted in cells by immunohis-tochemistry. AFP levels are normally very high in neonates and decreasewith time. Thismarker is particularly useful for assessing thepresence ofresidual or recurrent disease.

Thepostoperativehalf-life is about 6 days. Persistently high levelsmaybe an indication of the need for further surgical procedures orchemotherapy [6]. Other markers that may be elevated are β-humanchorionic gonadotropin (β-hCG), produced by choriocarcinomas, andrarely, carcinoembryonic antigen. Lactatedehydrogenase isomerof LDH-1is present in many tumors with the histologic features of an endodermalsinus tumor, yolk sac tumor, dysgerminoma, and choriocarcinoma.

3.2. Genetic

The genetic basis for teratoma is notwell understood and the clinicalusefulness unclear. Deletions on chromosome 1 and 6 were reported inchildren but noted on chromosome12 in adults. N-myc gene expressionwas noted in immature teratoma but not in the mature group [7].

3.3. Associated anomalies

Teratomas are mainly isolated lesions but may form part of theCurrarino triad (anorectalmalformation, sacral anomaly, and apresacralmass) as the presacralmass[8]. Other associated anomalies reported areurogenital (hypospadias, vesicoureteral reflux, and vaginal or uterineduplications), congenital dislocation of the hip, central nervous systemlesions (anencephaly, trigonocephaly, Dandy-Walker malformations,spina bifida, and myelomeningocele), Klinefelter's syndrome (stronglyassociated with mediastinal teratoma) and the very rare associationswith: trisomy 13, trisomy 21, Morgagni's hernia, congenital heartdefects, Beckwith–Wiedemann syndrome, pterygium, cleft lip andpalate, and rare syndromes, such as Proteus and Schinzel–Giedionsyndromes [9,10].

3.4. Saccrococcygeal teratoma

Sacrococcygeal teratoma (SCT) is the most common congenitaltumor and accounts for 35% to 60% of all teratomas. The estimatedincidence is 1 per 35,000 to 40,000 live births with a female-to-maleratio of 4:1 [11]. Altman has classified these tumors into four types [12]:

Type I the most common type are tumors that are predominantlyexternal with a minimal presacral component

Type II tumors are external but have a significant intrapelviccomponent

Type III tumors are external but pelvic and extend significantlyinto the abdomen

Type IV tumors are entirely presacral.

In recentdecades, an increasingnumber of sacrococcygeal teratomasare detected by antenatal ultrasonographic (US) examination of thefetus, especially where routine scans are performed at 20 weeksgestation such as in England and Wales (UK). Prenatal US is useful inmaking a differential diagnosis between sacrococcygeal teratoma,myelomeningocele, and other tumors. Antenatal ultrasound helps toestablish tumor extension into the pelvis and the presence or absence ofpolyhydramnios, fetal hydrops and intratumoral hemorrhage [13].Doppler ultrasound is the diagnostic tool, however fetal MRI may beused as an adjunct to prenatal scan for better definition of complexlesions and perioperative management [13,14] (Fig. 1A).

SCT is a highly vascular tumor and in large lesions the fetus maydevelop high cardiac output failure, anaemia and ultimately hydrops

with a mortality of almost 100% [15,16]. Fetal treatment of tumorresection or ablation of feeding vessel with fetoscopic laser therapy orradiofrequency has been attempted in hydropic patients with somesuccess [13,17–19].Caesarean section may be offered to patients withlarge tumors to avoid the risk of bleeding during delivery.

In the absence of prenatal scanning most sacrococcygeal teratomasare seen as a visible mass at birth, making the diagnosis obvious.Although many neonates with sacrococcygeal teratomas do not havesymptoms, some require intensive care because of prematurity, high-output cardiac failure, disseminated intravascular coagulation, andtumor rupture or bleeding within the tumor. Lesions with a largeintrapelvic component may cause urinary obstruction. An ultrasoundscan is a useful adjunct to the physical examination in evaluating lesionswith intrapelvic extension and evidence of meningomyelocoele. Thediagnosis of purely intrapelvic teratomasmay be delayed. Children haveconstipation, urinary retention, an abdominal mass, or symptoms ofmalignancy, such as failure to thrive [20].

Complete excision of the tumor with the coccyx is recommended assoon as the neonate is stable enough to undergo the procedure.Abdomino-perineal approach may be necessary for tumors with pelvicextension. Serum markers (alfa fetoprotein and beta HCG) before theoperation are helpful for later comparison.

Age is a predictor of malignancy in sacrococcygeal teratomas. Therisk of malignancy is less than 10% at birth but more than 75% after age1 year for sacrococcygeal tumors, with the exception of familialpresacral teratomas. The risk ofmalignancy also is high for incompletelyexcised lesions [21].

Functional results in survivors are excellent in most patients withAltmanType 1 and 2 lesions, however urinary and faecal incontinenceproblems and lower limb weakness have been recently reported inpatients with type 3 and 4 tumors [22].

Long term monitoring of all patients with physical examination,ultrasound scans and serummarkers, ismandatory for early detection ofrecurrences as well as assessment of urinary and bowel function [23].

Poor prognosis is noted in prenatal hydrops,dystocia,tumor rupture,prematurity, highly vascular lesion and lesions larger thansin size. In theabsence of severe prematurity and intrapartum complications, theprognosis is dependent on the presence of malignancy and is thereforerelated to age at operation, completeness of resection, tumor type andtumor stage [24].

3.5. Mediastinal teratoma

The mediastinum is the second most frequent site of extragonadalteratomas. Mediastinal teratomas occur in newborns to adolescents, andarise predominantly in the anterior mediastinum, occasionally in theposteriormediastinum, and rarely in the pericardial and intracardiac andpulmonary region.Most anteriormediastinal teratomasarediagnosedonprenatal scan. Large lesions may cause fetal hydrops or airwaycompression requiring strategies for fetal intervention or early delivery[25]. Mediastinal teratomas typically manifest on CT as a heterogeneousmass containing soft tissue, fluid, fat, or calcification. Some babies areasymptomatic anddiagnosis is knownprenatally ormade incidentally onchest X-ray. However, affected infants usually manifest symptoms suchas dyspnea, cough, or chest pain. When the tumor causes severerespiratory distress in neonates mimicking congenital diaphragmatichernia, emergency surgery to relieve lung compression and postopera-tive care supporting respiration are required.

Ultrasound, CT scan and MRI are suitable imaging modalities.Preoperative measurements of alfa feto protein tumor marker arenecessary for diagnosis and more importantly for postoperativemonitoring of tumor recurrence. Surgical approaches to mediastinalteratomas are either unilateral lateral thoracotomy or median sterno-tomy; the latter is necessary in some patients with large, bilaterallyinvasive lesions. Small lesions have been resected byusing video-assisted

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Sacrococcygeal teratoma

internal

external

A B

Fig. 1. A: Prenatal MRI showing sacrococcygeal teratoma with a small internal and large external component. B: Postnatal large bleeding sacrococcygeal teratoma.

645K. Lakhoo / Early Human Development 86 (2010) 643–647

thoracic surgery (VATS). Large lesions may cause airway compromiseand require intubation and care in the intensive care unit [26].

Intrapericardial lesions are rare but most commonly seen in utero orin the neonatal period. Presentation may be prenatal with evidence offetal hydrops or fetal distress, or postnatally with signs of massivepericardial effusion. Prenatal diagnosis may allow for early postnataltreatmentwith favourable outcome. Delay in diagnosismaybe fatal [27].

3.6. Testicular teratoma

Teratomas of the testes are the most common type of benignneoplasms in the neonatal testes. These tumors can be managedsuccessfully with radical orchiectomy and do not require any adjunctivetreatment. Small encapsulated cystic teratomas may also be enucleatedmuch like their ovarian counterpart; the cord should be occluded atraumatically until a frozen section confirms the benign nature of the

A B

teratoma

Fig. 2. A: Postnatal MRI showing a left ovarian teratoma w

lesion. However, for the purpose of treatment, all testicular tumors shouldbe taken as malignant unless proven otherwise on histopathology [28].

3.7. Ovarian teratoma (Fig. 2)

Mature teratoma, a benign neoplasm, is the single most commonovarian tumor and represents approximately 40% of all ovarian tumors.Itmaybecystic, solid ormixedwith calcificationnoted in50%of cases onplain abdominal radiograph. 10% are bilateral. Prenatal diagnosis of anintra-abdominal cyst or specific ovarian cystmaybemade at the routine20 week anomaly scan.

Abdominal pain, the presence of a mass, and occasionally an acuteabdomenasa result of torsionor ruptureof the tumor are knownclinicalpresentations. Some are discovered incidentally with imaging. Tumorsthat are predominantly cystic (dermoid cysts), may be safely excisedpreserving a rimof normalovarian tissue. Safety of laparoscopic excision

ith bony calcification. B: Massive ovarian teratoma.

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646 K. Lakhoo / Early Human Development 86 (2010) 643–647

is questioned since rupture of the cyst often occurs, leading to potentialperitoneal implantation of cells [29].

Solid teratomas are more often immature and the treatment ofchoice is salpingo oophorectomy. Chemotherapy is reserved for tumorswith higher grade of immaturity and rarely required in the neonatallesion. Serum alpha-fetoprotein levels (AFP) may be elevated preoper-atively and should be monitored after operation. In such cases carefulsectioning of the specimen may reveal microscopic foci of yolk sactumor; this does not alter management as long as AFP levels return tonormal. Normally elevated AFP in neonate should be taken intoconsideration before conclusions are drawn [29,30].

3.8. Gastric teratomas

Gastric teratomas are rare tumors accounting for less than 2% ofabdominal teratomas and 1% of all teratomas. They occur mainly inneonatal boys and are almost always benign in nature with an excellentprognosis. The tumor may be predominantly exogastric (67%) orendogastric (33%). The endogastric type grows into the lumen of thestomacherodesmucosa causinggastric outlet obstruction, hematemesisand melaena. The exogastric type is an exophytic mass in the lessercurvature or posterior wall of the stomach, and thewhole stomachmaybe involved. The exogastric variant may present with respiratorydistress and abdominal distension [31,32]. Diagnostic modalitiesinclude plain radiograph, US and CT scan and serum markers. Plainradiograph may show soft tissue mass with calcification in the upperabdomen. Surgical excision is curative. Recurrence and malignancy arerare, despite local infiltration or nodal metastasis. Follow-up includingAFP measurements is important [33].

Other rare sites of abdominal teratomas include liver, gallbladder,pancreas, kidney, intestine, bladder, prostate, uterus, mesentery,omentum, abdominal wall and diaphragm.

3.9. Retroperitoneal teratoma

These represent 5% of all childhood teratomas and occur outside thepelvis in the suprarenal location [34].The tumor presents as anabdominal mass with symptoms of vomiting and constipation.Diagnosis is made by imaging with calcification on plain radiograph,US and CT scan and serum markers. Surgical excision is often easilyperformed, and malignancy is uncommon. The retroperitoneum site isthe most common for the fetus in fetu malformations [34].

3.10. Intracranial teratoma

Congenital intracranial teratoma is a rare disease. A fetus with acongenital intracranial teratomausually presentswith a hydrocephalus.Intracranial teratomas generally present with symptoms of space-occupying lesions. These lesions account for only 2% to 4% of allteratomas, but they represent nearly 50% of brain tumors in the first2 months of life. Most are benign in neonates but malignant in olderchildren and young adults. These teratomas can appear in utero andcausemassive hydrocephalus. The pineal gland is themost common siteof origin, but intracranial teratomasmay be seen in different areas, suchas the hypothalamus, ventricles, cavernous sinus, cerebellum, andsuprasellar region [35,36].

3.11. Cervical teratomas

Cervical teratomas represent up to 8% of all teratomas. Large tumorscan be seen in utero with ultrasound and may require fetal interventionor an EXIT (EX-utero Intrapartum Treatment) procedure [37]. Thesetumors are initially seen as apartly or completely cystic neckmass,whichmay compromise the airway and require immediate intubation ortracheostomy. Extensionof tumor to themediastinumordisplacementofthe trachea may cause pulmonary hypoplasia and increase respiratory

morbidity and mortality. The tumor is usually well defined and maycontain calcifications. The differential diagnosis includes cystic hygroma,congenital goiter, foregut duplication cyst, and branchial cleft cyst.Investigation should include plain radiographs, US, and measurement ofAFPandβ-hCG, aswell as urinary catecholaminemetabolites. CT andMRImay be useful to establish the diagnosis and to define the anatomicrelations [38].

3.12. Craniofacial teratomas

Craniofacial teratomas include a spectrumof lesions thatmaybe life-threatening. The spectrum include epignathus (teratoma from palate),orbital, pharyngeal, oropharyngeal and middle ear teratoma [39].

Epignathus is the commonest craniofacial teratoma in the newborn.The terminology describes a tumor protruding from the mouth and itoriginates from the hard or soft palate close to Rathke's pouch.Polyhydramnios due to lack of fetal swallowing may alert thesonographer to the oral lesion. Airway management may be requiredat birth. The lesion is benign and surgical excision is the treatment ofchoice. Recurrence may occur with incomplete excision [40].

3.13. Miscellaneous sites

Teratomas have been reported in other sites, such as skin, parotid,vulva, perianal regionwell away from the coccyx, spinal canal, umbilicalcord (possibly associated with omphalocele), and placenta.

4. Key guidelines

1. Most neonatal teratomas are benign and are cured by surgicalexcision.

2. Incomplete resection or missed diagnosis may lead to malignantchange.

3. Prenatal diagnosis has improved management strategies for theselesions whereby fetal intervention may be required to preventhydrops fetalis or early delivery planned to avoid fetal comprimise.

4. Antenatal diagnosis also helps appropriate fetal counselling toprospective parents and planning of airway management at birthespecially with mediastinal and cervical lesions.

5. Alpha feto protein is a reliable tumor marker to detect recurrence ofthe disease so that appropriate management may be commenced.

6. Airway management is the most crucial aspect in the treatment ofcervical and mediastinal teratomas.

5. Research directions

1. Fetal intervention in cases with an otherwise hopeless prognosis.2. Fetal intervention in sacrococcygeal teratoma to prevent hydrops

fetalis.3. Refinement of the EXIT procedure to prevent morbidity and

mortality.4. Genetic basis for teratoma is not well understood and requires

further exploration.

References

[1] Virchow R. Ueber Die Sakralgeschwulst Des Schliewener Kindes. Klin Wochenschr1869;46:132.

[2] Isaacs Jr H. Perinatal (fetal and neonatal) germ cell tumors. J Pediatr Surg Jul2004;39(7):1003–13.

[3] Moore KL, Persaud TVN. The developing human: clinically oriented embryolo-gy7th edition. . Philadelphia: WB Saunders; 2003.

[4] Heerema-McKenney A, Harrison MR, Bratton B, Farrell J, Zaloudek C. Congenitalteratoma: a clinicopathologic study of 22 fetal and neonatal tumors. Am J SurgPathol Jan 2005;29(1):29–38 Review.

[5] McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal germ cell tumors: areview with emphasis on pathologic features, clinical prognostic variables, anddifferential diagnostic considerations. Adv Anat Pathol Mar 2007;14(2):69–92Review.

Page 5: Neonatal Teratomas

647K. Lakhoo / Early Human Development 86 (2010) 643–647

[6] Ishiguro T, Tsuchida Y. Clinical significance of serum alpha-fetoprotein subfractiona-tion in pediatric diseases. Acta Paediatr 1994;83:709–13.

[7] Harms D, Zahn S, Göbel U, Schneider DT. Pathology and molecular biology ofteratomas in childhood and adolescence. Klin Pädiatr Nov–Dec 2006;218(6):296–302.

[8] Sen G, Sebire NJ, Olsen O, Kiely E, Levitt GA. Familial Curranino syndromepresenting with peripheral primitive neuroectodermal tumour arising with asacral teratoma. Pediatr Blood Cancer 2008;50:172–5.

[9] Subbarao P, Bhatnagar V, Mitra DK. The association of sacrococcygeal teratomawith high anorectal and genital malformations. Aust NZ J Surg 1994;64:214–5.

[10] Zachariou Z, Krug M, Benz G, Daum R. Proteus syndrome associated with asacrococcygeal teratoma, a rare combination. Eur J Pediatr Surg Aug 1996;6(4):249–51.

[11] Swamy R, Embleton N, Hale J. Sacrococcygeal teratoma over two decades: birthprevalence, prenatal diagnosis and clinical outcomes. Prenat Diagn 2008;28:1048–51.

[12] Altman RP, Randolph JG, Lilly JR. Sacrococcygeal teratoma: American Academy ofPediatrics Surgical Section survey. J Pediatr Surg 1974;9:389–98.

[13] Hedrick HL, Flake AW, Crombleholme TM, Howell LJ, JohnsonMP,Wilson RD, et al.Sacrococcygeal teratoma: prenatal assessment, fetal intervention and outcome. JPediatr Surg Mar 2004;39(3):430–8 discussion 430-8.

[14] Danzer E, Hubbard AM, Hedrick HL, Johnson MP, Wilson RD, Howell LJ, et al.Diagnosis and characterization of fetal sacrococcygeal teratoma with prenatalMRI. AJR Am J Roentgenol Oct 2006;187(4):W350–6.

[15] Chisholm CA, Heider AL, Kuller JA, von Allmen D, McMahon MJ, Chescheir NC.Prenatal diagnosis and perinatal management of fetal sacrococcygeal teratoma.Am J Perinatol 1999;16:47–50.

[16] Adzick NS. Open fetal surgery for life threatening fetal anomalies. Semin FetalNeonatal Med 2010;15(1):1–8.

[17] Hecher K, Hackeloer B-J. Intrauterine endoscopic laser surgery for fetalsacrococcygeal teratoma. Lancet 1996;347:470.

[18] Paek BW, Jennings RW, Harrison MR, Filly RA, Tacy TA, Farmer DL, et al.Radiofrequency ablation of human fetal sacrococcygeal teratoma. Am J ObstetGynecol 2001;184:503–7.

[19] Ruano R, Duarte S, Zugaib M. Percutaneous laser ablation of sacrococcygealteratoma in a hydropic fetus with severe heart failure — too late for a surgicalprocedure? Fetal Diagn Ther 2009;25(1):26–30.

[20] Barksdale Jr EM, Obokhare I. Teratomas in infants and children. Curr Opin PediatrJun 2009;21(3):344–9 Review.

[21] Khalil BA, Aziz A, Kapur P, Humphrey G, Morabito A, Bruce J. Long-term outcomesof surgery for malignant sacrococcygeal teratoma: 20 year experience of a UKregional centre. Pediatr Surg Int Mar 2009;25(3):247–50.

[22] Draper H, Chitayat D, Ein SH, Langer JC. Long-term functional results followingresection of neonatal sacrococcygeal teratoma. Pediatr Surg Int Mar 2009;25(3):243–6.

[23] Tailor J, RoyPG,HitchcockR,GrantH, JohnsonP, JosephVT, et al. Long term functionaloutcome of sacrococcygeal teratom in a UK regional centre (1993–2006). PediatrHematol Oncol Mar 2009;31(3):183–6.

[24] Lakhoo K. Fetal counselling for congenital malformations. Pediatr Surg Int2007;23(6):509–19.

[25] Merchant AM, Hedrick HL, Johnson MP, Wilson RD, Crombleholme TM, Howell LJ,et al. Management of fetal mediastinal teratoma. J Pediatr Surg Jan 2005;40(1):228–31.

[26] Martino F, Avila LF, Encinas JL, Luis AL, Olivares P, Lassaletta L, et al. Teratoma ofthe neck and mediastinum in children. Pediatr Surg Int Aug 2006;22(8):627–34Epub 2006 Jul 13.

[27] Gobbi D, Rubino M, Chiandetti L, Zanon GF, Cecchetto G. Neonatal intrapericardialteratoma: a challenge for the pediatric surgeon. J Pediatr Surg Jan 2007;42(1):E3–6.

[28] Oottamasathien S, Thomas JC, Adams MC, DeMarco RT, Brock III JW, Pope IV JC.Testicular tumours in children: a single institution experience. BJU Int May2007;99(5):1123–6.

[29] Panteli C, Curry J, Kiely E, Pierro A, de Coppi P, Anderson J, et al. Ovarian germ celltumours: a 17-year study in a single unit. Eur J Pediatr Surg Apr 2009;19(2):96–100.

[30] De Backer A, Madern GC, Oosterhuis JW, Hakvoort-Cammel FG, Hazebroek FW.Ovarian germ cell tumors in children: a clinical study of 66 patients. Pediatr BloodCancer Apr 2006;46(4):459–64.

[31] Herman TE, Siegel MJ. Congenital gastric teratoma. J Perinatol Nov 2008;28(11):786–7.

[32] Saleem SM, Hussain S, Nazir Z. Gastric teratoma — a rare benign tumour ofneonates. Ann Trop Paediatr Dec 2003;23(4):305–8.

[33] Sarin YK, Agarwal LD, Jhamaria VN, Goyal RB, Sharma R, Shekhawat NS. Immaturegastric teratoma. Indian J Pediatr Nov–Dec 1997;64(6):896–8.

[34] Eyssartier E, Harper L, Michel JL, Rivière JP, Vanderbecken S, De Napoli-Cocci S.Rapidly growing mature retroperitoneal teratomas. J Pediatr Hematol Oncol Sep2009;31(9):705–6.

[35] Köken G, Yilmazer M, Sahin FK, Coşar E, Aslan A, Sahin O, et al. Prenatal diagnosisof a fetal intracranial immature teratoma. Fetal Diagn Ther 2008;24(4):368–71.

[36] Noudel R, Vinchon M, Dhellemmes P, Litré CF, Rousseaux P. Intracranial teratomasin children: the role and timing of surgical removal. J Neurosurg Pediatr Nov2008;2(5):331–8.

[37] Bouchard S, Johnson MP, Flake A, et al. The EXIT procedure: experience andoutcome in 31 cases. J Pediatr Surg 2002;37:418–26.

[38] Herman TE, Siegel MJ. Cervical teratoma. J Perinatol Sep 2008;28(9):649–51.[39] Anderson PJ, David DJ. Teratomas of the head and neck region. J Craniomaxillofac

Surg Dec 2003;31(6):369–77.[40] Kumar B, Sharma SB. Neonatal oral tumors: congenital epulis and epignathus. J

Pediatr Surg Sep 2008;43(9):e9–e11 Review.